NCI CANCERLIT^® Search: Kidney (Renal Cell) Cancer - September 2001

Last Modified: November 1, 2001

Proliferating cell nuclear antigen and epidermal growth factor receptor (EGFr) status in renal cell carcinoma patients with polysomy of chromosome 7.
The generation and characterization of a cell line derived from a sporadic renal angiomyolipoma: use of telomerase to obtain stable populations of cells from benign neoplasms.
Modulation of IgG and complement receptor expression of phagocytes in kidney cancer patients during treatment with interferon-alpha.
[Histologic classification of kidney tumors for clinical practice in adults]
Cadherins and integrins in renal cell carcinoma: an immunohistochemical study.
Parvalbumin is constantly expressed in chromophobe renal carcinoma.
Extensive necrosis in renal cell carcinoma specimens: potential clinical and prognostic implications.
[Radical nephrectomy for the kidney tumor with the thrombus invading vena cava inferior]
Treatment of kidney cancer with autologous tumor cell vaccines of short-term cell lines derived from renal cell carcinoma.
The pVHL-associated SCF ubiquitin ligase complex: molecular genetic analysis of elongin B and C, Rbx1 and HIF-1alpha in renal cell carcinoma.
Renal cell cancer correlated with occupational exposure to trichloroethylene.
Rhabdoid tumour of the kidney: imaging findings.
Open surgical partial nephrectomy.
Laparoscopic radical nephrectomy.
Laparascopic partial nephrectomy.
Energy-based renal tumor ablation: a review.
Vaccine and gene therapy of renal cell carcinoma.
Cytokine therapy for metastatic renal cell carcinoma.
Biology of renal cell carcinoma: changing concepts in classification and staging.
Molecular markers for renal cell carcinoma: impact on diagnosis and treatment.
Surgical approaches to venous tumor thrombus.
The role of radical nephrectomy in metastatic renal cell carcinoma.
[Laparoscopy-assisted total nephroureterectomy for renal pelvic and/or lower ureteral cancer]
Gene expression profiling of clear cell renal cell carcinoma: gene identification and prognostic classification.
Birt-Hogg-Dube syndrome: mapping of a novel hereditary neoplasia gene to chromosome 17p12-q11.2.
Patterns of recurrence in renal cell carcinoma: manifestations on helical CT.
Feasibility of prolonged use of interferon-alpha in metastatic kidney carcinoma: a phase II study.
Hypomethylation of the MN/CA9 promoter and upregulated MN/CA9 expression in human renal cell carcinoma.
Validation of the ucla integrated staging system for patients with renal cell carcinoma.
Tuberous sclerosis. Part II. Musculoskeletal and visceral findings.
Phase II evaluation of paclitaxel, alpha-interferon, and cis-retinoic acid in advanced renal cell carcinoma.
Renal cell carcinoma: incidental detection and pathological staging.
Renal cell carcinoma: incidental detection and pathological staging. 2000; 45(5):291-295.
Differential expression of cytokines and cytokine receptors in renal cell carcinoma.
[Chromophobe cell renal cancer, a distinct entity. Report of a series of 35 cases]
[Retrospective comparative study of extended nephrectomies by surgery and by retroperitoneal laparoscopy]
[Interleukin-6 and bone metastasis of renal cancer: molecular bases and therapeutic implications]
[Genetics of renal tumors]
Renal cell carcinoma: evaluation of the 1997 TNM system and recommendations for follow-up after surgery.
VHL gene alterations in renal cell carcinoma patients: novel hotspot or founder mutations and linkage disequilibrium.

CancerMail from the National Cancer InstituteKidney (Renal Cell) Cancer - September 2001

1
UI - 21261630
AU - Amare Kadam PS; Varghese C; Bharde SH; Narasimhamoorthy NK; Desai S; Advani SH; Havaldar R; Kulkarni JN
TI - Proliferating cell nuclear antigen and epidermal growth factor receptor (EGFr) status in renal cell carcinoma patients with polysomy of chromosome 7.
SO - Cancer Genet Cytogenet 2001 Mar;125(2):139-46
AD - Cytogenetic Laboratory, Department of Medical Oncology, Tata Memorial Hospital, Dr. Ernest Borges Marg, Parel, 400012, Mumbai, India.
We investigated 40 cases of renal cell carcinoma (RCC) to study the polysomy 7 status in papillary and clear-cell types (nonpapillary RCC) and relationship with clinical, pathological, and biological features such as grade, stage, tumor proliferation rate (PCNA expression) and epidermal growth factor receptor (EGFr) expression and thereby to understand the prognostic significance of polysomy 7 and EGFr expression. In a prospective study, chromosome 7 copy number was analyzed in tumor cells by using fluorescence in situ hybridization (FISH) with an alpha-satellite DNA probe for chromosome 7. Both proliferating cell nuclear antigen (PCNA) and EGFr expression were examined in paraffin sections by immunostaining. The relationship between clinicopathological and clinicobiological parameters was evaluated by appropriate statistical methods. Polysomy 7 was present in 100% of papillary and 56.2% of clear-cell types RCC. In clear-cell RCC, in comparison with polysomy 7-dominant (D) category (20-50% polysomy-7 cells), polysomy 7-major (M) category (>50% polysomy 7 cells) was associated with higher tumor grade (P = 0.05). Polysomy 7 was also correlated with stage of the disease (P = 0.006). The PCNA index ranged between 12.8-89.6% and was comparatively high in high-grade tumors (P = 0.001). The PCNA index was also correlated with polysomy 7 (P = 0.002), and the association was stronger in tumors with polysomy M versus polysomy D category (P = 0.02). The EGFr expression did not correlate with either grade, stage, PCNA, or polysomy 7. The correlation of polysomy 7 with less favorable prognostic factors such as higher tumor grade, stage, and higher proliferative index in the present study indicates that polysomy 7 might be used as a prognostic predictor in clear-cell RCC. Evaluation of clinical end points will confirm the prognostic potential of the genetic marker polysomy 7 in our study.

2
UI - 21378005
AU - Arbiser JL; Yeung R; Weiss SW; Arbiser ZK; Amin MB; Cohen C; Frank D; Mahajan S; Herron GS; Yang J; Onda H; Zhang HB; Bai X; Uhlmann E; Loehr A; Northrup H; Au P; Davis I; Fisher DE; Gutmann DH
TI - The generation and characterization of a cell line derived from a sporadic renal angiomyolipoma: use of telomerase to obtain stable populations of cells from benign neoplasms.
SO - Am J Pathol 2001 Aug;159(2):483-91
AD - Department of Dermatology, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA. jarbise@emory.edu
Angiomyolipomas are benign tumors of the kidney derived from putative perivascular epithelioid cells, that may undergo differentiation into cells with features of melanocytes, smooth muscle, and fat. To gain further insight into angiomyolipomas, we have generated the first human angiomyolipoma cell line by sequential introduction of SV40 large T antigen and human telomerase into human angiomyolipoma cells. These cells show phenotypic characteristics of angiomyolipomas, namely differentiation markers of smooth muscle (smooth muscle actin), adipose tissue (peroxisome proliferator-activator receptor gamma, PPARgamma), and melanocytes (microophthalmia, MITF), thus demonstrating that a single cell type can exhibit all of these phenotypes. These cells should serve as a valuable tool to elucidate signal transduction pathways underlying renal angiomyolipomas.

3
UI - 21388257
AU - Salminen E; Kankuri M; Nuutila J; Lilius EM; Pellimiemi TT
TI - Modulation of IgG and complement receptor expression of phagocytes in kidney cancer patients during treatment with interferon-alpha.
SO - Anticancer Res 2001 May-Jun;21(3B):2049-55
AD - Department of Oncology and Radiotherapy, University of Turku, Finland.
BACKGROUND: The mode of action of interferon involves both direct cytotoxic and antiproliferative effects on the tumour cell and indirect effects that facilitate immune detection by the host. Among the immunological effects of interferon-alpha is the activation of monocytes. As opsonin receptors are crucial in the function of phagocytes, e.g. monocytes and neutrophils, their modulation by interferon-alpha (INF-alpha) merit to be further clarified. We hypothesised that the role of phagocytes in defence against cancer is reflected in the expression of opsonin receptors for IgG and complement, which further could be modified by INF-alpha. PATIENTS AND METHODS: The expression of the receptors for IgG and complement was studied in neutrophils and monocytes from blood samples of 18 kidney cancer patients treated with INF-alpha and from 39 healthy individuals. Blood samples were collected prior/to and during treatment with INF-alpha, 4.5 to 13.5 MU t.d.w., subcutaneously. After lysing the red blood cells, the samples were incubated with fluorochrome conjugated monoclonal antibodies specific for IgG (Fc gammaRI, -RII and -RIII) and complement (CR1, CR3) receptors and then analysed in flow cytometry. The results were given as the mean log fluorescence intensity (a measure of receptor number) and as the proportion of receptor-positive cells. In the in vitro experiments, the direct effect of interferon-alpha on the receptors of neutrophils and monocytes was studied. RESULTS: In patients before any treatment, the expression of CR3 and Fc gammaRI receptors in neutrophils and all receptors except Fc gammaRIII in monocytes was significantly raised when compared to the controls. Treatment with INF-alpha, induced statistically significant; transient changes in CR1-receptor expression in neutrophils and Fc gammaRI expression in monocytes. Incubation of blood cells with INF-alpha in vitro confirmed the induction of CR1 receptors in neutrophils. CONCLUSION: Changes in receptor expression reflect the inflammatory activation of phagocytes in metastatic kidney cancer. The pattern of receptor expression differs from that observed in infectious diseases. Interferon-alpha both in vivo and in vitro modulates the expression of phagocytic receptors.

4
UI - 21395227
AU - Hora M; Hes O; Michal M
TI - [Histologic classification of kidney tumors for clinical practice in adults]
SO - Cas Lek Cesk 2001 Jun 21;140(12):364-9
AD - Urologicka klinika LF UK a FN, Plzen. horam@fnplzen.cz
Kidney tumors represent a wide scale of histological observations. However, only angiomyolipoma can be recognised preoperatively from results of the graphical examination. Other types can be recognised only on the bases of histological examination. Completely benign tumor is oncocytoma (it represents about 5% of all kidney tumors). Angiomyolipoma (2%) is also benign, though some case reports describing its malign transformation has been published. Angiomyolipoma under 4 cm can be only monitored, the larger tumors should be resected or selectively embolised the arterial blood supply to prevent spontaneous rupture. From the group of benign tumors only cystic nephroma can be diagnosed more often (up to 1%). One of the criteria for diagnosing the renal cortical adenoma is its size under 5 mm. That is why any adenoma, which could be diagnosed by means of graphical examination and therefore clinically significant does not exist. Most of tumors are malign epithelial tumors--renal carcinomas (RC). The are classified according Heidelberg classification into 5 elementary types: clear cell, papillary, chromophobe, originating form collecting ducts and not classifiable. Clear cell (conventional) renal carcinoma (CRC) comes most often (70 to 80%), its malign potential rise with increased size of tumor and with the gradient. Five-year survival is achieved in 30-50%. Granular form of CRC carcinoma (7% of all CRC) is the equivalent of poorly differentiated PRC and it has an adverse prognosis. In contrary, the cystic form of CRC (about 6%) in benign. Papillary form of RC has the five-year survival in 84%, malignant are only tumors poorly differentiated. These are tumors with extensive necroses, which brings a fragile consistency and they can be distinguished by graphical examination. Chromophobe type of RC (5%) has the five-year survival in 90%. Poor prognosis has its sarcomatoid form, which can originate from any RC, but most frequently it is derived from the chromophobe type. The form originating from collecting ducts is highly infrequent and very malignant with the five-year survival in 20% only. The unclassified form of RC (3-5%) includes tumors not suiting to the criteria of the previous RC. Other primary renal malignant tumors (sarcomas, Wilms' tumor of adults, medullar carcinoma, carcinoid) are very rare. Comparatively frequent are metastases of other tumors (namely that of lung carcinoma) and renal impairment in leukemia, which are complication not often met by urologist.

5
UI - 21395122
AU - Markovic-Lipkovski J; Brasanac D; Muller GA; Muller CA
TI - Cadherins and integrins in renal cell carcinoma: an immunohistochemical study.
SO - Tumori 2001 May-Jun;87(3):173-8
AD - Institute of Pathology, School of Medicine, University of Belgrade, Yugoslavia. saog@beotel.yu
AIMS AND BACKGROUND: The aim of this study was to determine the expression of cadherins and integrins in renal cell carcinoma (RCC) and their relationship with tumor morphology and TNM status. METHODS: Cadherin and integrin expression was investigated using an indirect immunoperoxidase technique, applying antibodies to E-, N-, P- and VE-cadherin and to alpha1, alpha2, alpha3, alpha4, alpha5, alpha6, and alpha(v) integrin subunits. Correlation of semiquantitatively scored adhesion molecule levels with histopathological parameters (cytology, growth pattern, nuclear grade) and TNM status was performed for 24 RCCs (17 clear cell, 3 granular, 3 spindle cell and 1 chromophobe cell type according to the WHO classification). RESULTS: E-cadherin and N-cadherin were present in most cases (88% and 67%, respectively) and were usually coexpressed. T3 RCCs displayed higher E-cadherin and N-cadherin levels than T1/T2 tumors regardless of tumor grade, suggesting that impairment of their function might exist without actual loss from tumor cells. P-cadherin was found focally in two RCCs only, while VE-cadherin was present on stromal vessel endothelium in five tumors, showing no differences with regard to cell type, growth pattern, tumor grade or TNM status. All integrins were present in the studied RCCs (ranging from 12% for alpha5 to 79% for alpha3), including those that are normally absent from adult kidney tissue (alpha4 and alpha5). Tumors of higher grade showed increased alpha(v) and decreased alpha6 levels, while RCCs with metastases less often showed diffuse alpha3 presence and never expressed alpha5 integrin. CONCLUSIONS: Our results suggest that the level of expression of N-cadherin and some integrins (most notably alpha3, alpha6 and alpha5) is associated with the capacity of RCC for local and distant spread, regardless of tumor grade.

6
UI - 21396382
AU - Martignoni G; Pea M; Chilosi M; Brunelli M; Scarpa A; Colato C; Tardanico R; Zamboni G; Bonetti F
TI - Parvalbumin is constantly expressed in chromophobe renal carcinoma.
SO - Mod Pathol 2001 Aug;14(8):760-7
AD - Dipartimento di Patologia-Sezione Anatomia Patologica, Universita di Verona, Via delle Menegone, 10, Verona 37134, Italy. guidomart@yahoo.com
Chromophobe renal carcinoma is composed of neoplastic cell showing several features similar to those found in the intercalated cells of the collecting ducts. Because the distal nephron expresses calcium-binding proteins playing a role in calcium homeostasis, we reasoned that these proteins could be expressed by chromophobe carcinoma and therefore represent a diagnostic marker. We studied the immunohistochemical expression of different calcium-binding proteins (parvalbumin, calbindin-D28K, and calretinin) in 140 renal tumors, including 75 conventional (clear cell) carcinomas, 32 chromophobe carcinomas, 17 papillary renal cell carcinomas, and 16 oncocytomas. Parvalbumin was strongly positive in all primary chromophobe carcinomas and in one pancreatic metastasis; it was positive in 11 of 16 oncocytomas and absent in conventional (clear cell) and papillary renal cell carcinomas, either primary or metastatic. Calbindin-D28K and calretinin were negative in all tumors, with the exception of two chromophobe carcinomas, four oncocytomas, and two papillary renal cell carcinomas showing inconspicuous calretinin expression. Our data demonstrate that parvalbumin may be a suitable marker for distinguishing primary and metastatic chromophobe carcinoma from conventional (clear cell) and papillary renal cell carcinoma. Moreover, they suggest a relationship between chromophobe renal carcinoma and renal oncocytoma and indicate that chromophobe carcinoma exhibits differentiation toward the collecting-duct phenotype.

7
UI - 21411127
AU - Leibovitch I; Lev R; Mor Y; Golomb J; Dotan ZA; Ramon J
TI - Extensive necrosis in renal cell carcinoma specimens: potential clinical and prognostic implications.
SO - Isr Med Assoc J 2001 Aug;3(8):563-5
AD - Department of Urology, Sheba Medical Center, Tel-Hashomer, Israel. ilanl1@isdn.net.il
BACKGROUND: Extensive necrosis is rare in primary renal cell carcinoma. This finding may reflect the biological characteristics of the carcinoma and therefore could be of prognostic and clinical value. OBJECTIVES: To assess the incidence of necrosis in renal cell carcinoma and its potential prognostic value. METHODS: We conducted a consecutive retrospective study of 173 patients after radical nephrectomy for renal cell carcinoma. Clinical and pathological data were collected from hospital medical records and compiled into a computerized database. RESULTS: Extensive necrosis was found in 31 tumor specimens (17.9%). Univariate analysis showed that the specimens with extensive necrosis were significantly larger and manifested more perirenal and venous extension than the tumors without necrosis. The size of the renal tumor was the only parameter that remained significant in multivariate analysis (P = 0.0001). Overall disease-free survival did not differ significantly between patients with necrotic tumors and those without (68% and 66% respectively). CONCLUSIONS: The finding of extensive necrosis in renal cell carcinoma specimens does not seem to be related to tumor biology but rather may reflect the relation between size and vascularity of the tumor.

8
UI - 21141612
AU - Pereverzev AS; Lupal'tsov VI; Shchukin DV; Pereverzev IuA
TI - [Radical nephrectomy for the kidney tumor with the thrombus invading vena cava inferior]
SO - Klin Khir 2000 Dec;(12):49-53
The results of treatment were analyzed in 92 patients with the kidney tumor in whom the thrombus invasion into vena cava inferior was revealed. Ultrasonographic scanning and magnetic resonance tomography were most informative methods in the diagnosis. The staging of the tumoral thrombus invasion was elaborated depending on which the surgical tactics was choosen. The procedure technique was depicted and the operations schemes were adduced. The vena cava thrombectomy performance is absolutely indicated in patients without metastases in lymph nodes and distant organs. The five-year survival index for this patients was 55-60%.

9
UI - 21175027
AU - Dillman RO; Barth NM; VanderMolen LA; Garfield DH; De Leon C; O'Connor AA; Mahdavi K; Nayak SK
TI - Treatment of kidney cancer with autologous tumor cell vaccines of short-term cell lines derived from renal cell carcinoma.
SO - Cancer Biother Radiopharm 2001 Feb;16(1):47-54
AD - Hoag Cancer Center, One Hoag Drive, Building 41, Newport Beach, California 92658, USA. rdillman@hoaghospital.org
BACKGROUND: We established short-term cultures of autologous tumors from patients with renal carcinoma for use as active specific immunotherapy (i.e., autologous vaccine). METHODS: Between 9/91 and 9/99 the cell biology laboratory of the Hoag Cancer Center received 69 kidney tumor samples that had been surgically excised, including 43 primary tumors and 26 metastatic lesions. Efforts were made to establish short-term tumor cell cultures to use as autologous tumor cell vaccines. Prior to treatment, patients underwent a baseline skin test for delayed tumor hypersensitivity (DTH) and then received s.c. injections of 10 million irradiated tumor cells that were given with various adjuvants weekly x3 and then monthly x5. RESULTS: Cell lines were established for 55/69 patients (80%) including 36/43 (84%) from primary tumors and 19/26 (73%) from distant metastases. Vaccines were prepared for 41 patients; 27 were treated. At the time of this analysis, follow up data was available for 26 patients with a median follow up > 5 years. Treatment was well-tolerated. Of 10 patients who had no evident disease at the time of treatment, nine were alive 1-8 years later; 5/8 had conversion of their DTH test from negative to positive. For 16 patients with measurable metastatic disease at the time of treatment, there were no objective tumor responses; their median survival was 5.0 months. Among these 16 patients, only 1/8 DTH tests converted, but three had a positive baseline DTH test; one was previously treated with interleukin-2 and tumor infiltrating lymphocytes and two others were previously treated with autolymphocyte therapy. CONCLUSIONS: Vaccine therapy with short-term cultures of autologous tumor cells is feasible, well-tolerated and associated with conversion of DTH and long-term survival in patients who are free of disease at the time treatment is initiated. However, significant anti-tumor responses were not seen in patients with measurable disease at the time vaccine treatment was initiated.

10
UI - 21417656
AU - Clifford SC; Astuti D; Hooper L; Maxwell PH; Ratcliffe PJ; Maher ER
TI - The pVHL-associated SCF ubiquitin ligase complex: molecular genetic analysis of elongin B and C, Rbx1 and HIF-1alpha in renal cell carcinoma.
SO - Oncogene 2001 Aug 16;20(36):5067-74
AD - Section of Medical & Molecular Genetics, Division of Reproductive and Child Health, University of Birmingham, Birmingham, B15 2TT, UK.
The VHL gene product (pVHL) forms a multimeric complex with the elongin B and C, Cul2 and Rbx1 proteins (VCBCR complex), which is homologous to the SCF family of ubiquitin ligase complexes. The VCBCR complex binds HIF-1alpha and HIF-2alpha, transcription factors critically involved in cellular responses to hypoxia, and targets them for ubiquitin-mediated proteolysis. Germline mutations in the VHL gene cause susceptibility to haemangioblastomas, renal cell carcinoma (RCC), phaeochromocytoma and other tumours. In addition somatic inactivation of the VHL gene occurs in most sporadic clear cell RCC (CC-RCC). However, the absence of somatic VHL inactivation in 30-40% of CC-RCC implies the involvement of other gatekeeper genes in CC-RCC development. We reasoned that in CC-RCC without VHL inactivation, other pVHL-interacting proteins might be defective. To assess the role of elongin B/C, Rbx1 and HIF-1alpha in RCC tumorigenesis we (a) mapped the genes to chromosomes 8q(cen) (elongin C), 16p13.3 (elongin B) and 22q11.2 (Rbx1) by FISH, monochromosomal somatic cell hybrid panel screening and in silico GenBank homology searching; (b) determined the genomic organisation of elongin C (by direct sequencing of PAC clones), Rbx1 and elongin B (by GenBank homology searching); and (c) performed mutation analysis of exons comprising the coding regions of elongins B, C and Rbx1 and the oxygen-dependent degradation domain of HIF-1alpha by SSCP screening and direct sequencing in 35 sporadic clear cell RCC samples without VHL gene inactivation and in 13 individuals with familial non-VHL clear cell RCC. No coding region sequence variations were detected for the elongin B, elongin C or Rbx1 genes. Two amino acid substitutions (Pro582Ser and Ala588Thr) were identified in the oxygen-dependent degradation/pVHL binding domain of HIF-1alpha, however neither substitution was observed exclusively in tumour samples. Association analysis in panels of CC-RCC and non-neoplastic samples using the RFLPs generated by each variant did not reveal allelic frequency differences between RCC patients and controls (P>0.32 by chi-squared analysis). Nevertheless, the significance of these variations and their potential for modulation of HIF-1alpha function merits further investigation in both other tumour types and in non-neoplastic disease. Taken together with our previous Cul2 mutation analysis these data suggest that development of sporadic and familial RCC is not commonly contributed to by genetic events altering the destruction domain of HIF-1alpha, or components of the HIF-alpha destruction complex other than VHL itself. Although (a) activation of HIF could occur through mutation of another region of HIF-a, and (b) epigenetic silencing of elongin B/C, Cul2 or Rbx1 cannot be excluded, these findings suggest that pVHL may represent the sole mutational target through which the VCBR complex is disrupted in CC-RCC. HIF response is activated in CC-RCC tumorigenesis.

11
UI - 21213082
AU - Mandel JS
TI - Renal cell cancer correlated with occupational exposure to trichloroethylene.
SO - J Cancer Res Clin Oncol 2001 Apr;127(4):265-8

12
UI - 21220174
AU - Han TI; Kim MJ; Yoon HK; Chung JY; Choeh K
TI - Rhabdoid tumour of the kidney: imaging findings.
SO - Pediatr Radiol 2001 Apr;31(4):233-7
AD - Department of Diagnostic Radiology, Eulji University School of Medicine, 24-14, Mok-Dong, Jung-Gu, Taejon 301-726, South Korea. tihan@emc.eulji.ac.kr
BACKGROUND: Rhabdoid tumour of the kidney (RTK) is a rare tumour, but it is the most aggressive malignant neoplasm of the kidney in children. OBJECTIVE: To analyse the radiological findings of RTK in children. MATERIALS AND METHODS: The clinical and radiological findings in seven children (age range 6 months to 4.7 years; median 18 months) with pathologically proven RTK were retrospectively reviewed. We analysed tumour size, tumour location, tumour margin, subcapsular haematoma, tumour necrosis, haemorrhage, calcification and lymphadenopathy. RESULTS: Tumour size varied from 5 to 12 cm. Four tumours were located mainly in the central portion of the kidney, while three tumours were mainly sited peripherally. The margins of the tumour were ill-defined in four (57%) of seven cases, a lobulated tumour surface was depicted in all seven (100%), subcapsular haematoma was present in four (57%), tumour necrosis or haemorrhage in seven (100%), calcifications in three (43%) and retroperitoneal lymphadenopathy in four (57%). CONCLUSIONS: Imaging findings of RTK are subcapsular haematoma, a lobulated surface of the tumour, calcification and tumour necrosis or haemorrhage.

13
UI - 21253725
AU - Ghavamian R; Zincke H
TI - Open surgical partial nephrectomy.
SO - Semin Urol Oncol 2001 May;19(2):103-13
AD - Department of Urology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, USA.
The goals of conservative resection of renal cell carcinoma are complete local surgical removal of the malignancy and preservation of adequate renal function. This is a delicate balance, which makes renal preserving surgery at times both challenging and controversial. Surgical management of renal cell carcinoma remains the most effective curative management. The increased use of cross-sectional imaging has led to an increased detection of incidental renal cell carcinomas at an earlier stage. The indications of nephron-sparing surgery (NSS) have evolved in the past decade. Clinically, there are scenarios where nephron-sparing surgery is absolutely indicated. However, in the setting of a normal contralateral kidney, radical nephrectomy is still considered by many to be the treatment of choice for localized renal cell carcinoma. There is now growing evidence that in the correct patient, the use of NSS in the above-mentioned situation is justified. Very recent data indicate that NSS provides effective and equivalent oncologic treatment for most renal cell carcinomas especially those 4 cm or smaller. Refined surgical techniques and new studies regarding the earlier diagnosis and biology of renal cell carcinoma, true incidence of occult multifocality, and comparable morbidity with radical nephrectomy make NSS an attractive tool in the armamentarium of the urologic surgeon.

14
UI - 21253726
AU - Zisman A; Pantuck AJ; Belldegrun AS; Schulam PG
TI - Laparoscopic radical nephrectomy.
SO - Semin Urol Oncol 2001 May;19(2):114-22
AD - Department of Urology, University of California School of Medicine, Los Angeles 90095-1738, USA.
Most of the open renal procedures have been duplicated or approximated by laparoscopy. Past concerns about increased operative time, cost, resection completeness, and port site metastases are being overruled or put into perspective as experience with laparoscopic radical nephrectomy (LRN) is gained: necessary skills can be acquired, operative times are approaching those for open procedure, and a 14% difference in cost is counterbalanced by reduced postoperative expenditures. Moreover, LRN is acknowledged by its quality-of-life advantages-reduced morbidity and improved cosmetic outcome. Disease-free rate with LRN at last follow-up is 100% for TNM stage I and 89% +/- 6.6 for stage II (1997 classification). Complications are acceptable with an 8% to 35% incidence of minor complications and a 3% to 19% incidence of severe complications. Conversion to an open procedure occurs in 0% to 10% of cases. The procedure's limitations and the appropriate criteria for patient selection are evident. The learning process is believed to last for approximately 20 procedures and patient selection is based on both clinical criteria and one's insight on his location on the learning curve. Therefore, LRN is becoming the treatment of choice for most TNM stages I and II renal tumors. Moreover, recent data advocating pre-immunotherapy nephrectomy in metastatic patients may permit laparoscopic nephrectomy to further benefit selected metastatic patients by potentially shortening the time interval from nephrectomy to immunotherapy and improving immune responsiveness.

15
UI - 21253727
AU - Hollenbeck BK; Wolf JS Jr
TI - Laparascopic partial nephrectomy.
SO - Semin Urol Oncol 2001 May;19(2):123-32
AD - Department of Surgery, University of Michigan, Ann Arbor, USA.
The role of laparoscopy in urologic surgery has greatly increased over the past decade as has the popularity of elective nephron-sparing surgery. The emergence of these trends in conjunction with improvements in equipment and expertise has led to the increasing application of laparoscopic partial nephrectomy. Initially, this modality was applied in patients with benign diseases, such as chronic pyelonephritis and calculus disease with associated atrophy. Concerns of tumor spillage and local-regional control precluded the application of the laparoscopic modality to small, indeterminate renal masses. However, increasing experience with the technique and advances in intraoperative imaging have prompted its use in removing small renal masses. Herein, we describe the indications for laparoscopic partial nephrectomy, the two approaches (transperitoneal and extraperitoneal) to gain access to the kidney, current options to assist in controlling intraoperative hemorrhage, a comprehensive assessment of the results for benign and malignant resections, and an examination of the similarities and contrasts between open and laparoscopic techniques.

16
UI - 21253728
AU - Murphy DP; Gill IS
TI - Energy-based renal tumor ablation: a review.
SO - Semin Urol Oncol 2001 May;19(2):133-40
AD - Section of Laparoscopic and Minimally Invasive Surgery, Urological Institute, The Cleveland Clinic Foundation, OH 44195, USA.
The trend toward minimally invasive options in the management of renal tumors has prompted interest in energy-based ablation techniques as a possible alternative to radical or partial nephrectomy in select patients. Such techniques include radiofrequency thermal ablation, microwave thermotherapy, laser interstitial thermal therapy, high intensity focused ultrasound, interstitial photon radiation ablation, and cryoablation. This review describes the current status of these techniques as they apply to the management of renal tumors.

17
UI - 21253729
AU - Gitlitz BJ; Belldegrun AS; Figlin RA
TI - Vaccine and gene therapy of renal cell carcinoma.
SO - Semin Urol Oncol 2001 May;19(2):141-7
AD - Department of Medicine, University of California, School of Medicine, Los Angeles 90095-7059, USA.
The concept of tumor vaccines is not new. However, advances in gene transfer technology, tumor immunology, molecular biology, and methods of monitoring antitumor response, have allowed for novel, more specific vaccine approaches. For example, first-generation tumor vaccines were composed of whole inactivated cancer cells, or tumor lysates (Tuly) given together with immune adjuvants like bacillus Calmette-Guerin (BCG). Current strategies include tumor cells modified with genes encoding molecules necessary to stimulate a cytotoxic T cell response, such as cytokine genes, foreign HLA genes, tumor-associated antigen (TAA) genes, and even costimulatory molecules. Activation of cellular immunity requires at least three synergistic signals including presentation of specific tumor antigens, costimulatory signals (B7 molecules), and propagation of the immune response via cytokine release. In general, tumor cells often fail to demonstrate any of these immunostimulatory properties. Dendritic cell-based vaccines are gaining popularity as these cells can properly present TAA to the immune system, thus circumventing the poor antigen-presenting qualities of tumor cells. Dendritic cells can be "loaded" with TAA or other molecules either by their natural endocytotic capabilities, or by genetic modification.

18
UI - 21253730
AU - Bukowski RM
TI - Cytokine therapy for metastatic renal cell carcinoma.
SO - Semin Urol Oncol 2001 May;19(2):148-54
AD - Experimental Therapeutics, The Cleveland Clinic Taussig Cancer Center, OH, USA.
Cytokine therapy for patients with metastatic renal cancer is based on observations suggesting this neoplasm may be responsive to immunotherapy. Two cytokines, interferon-alpha (IFN-alpha) and interleukin 2 (IL-2) produce tumor regressions in 10% to 15% of patients with metastatic disease. Randomized trials demonstrate a modest survival advantage for patients treated with IFN-alpha. Combinations of IL-2 and IFN-alpha appear to be associated with improved response rates, but no demonstrable effect on survival. Additions of other cytokines (eg, GM-CSF) or chemotherapy to this combination has been investigated, but results do not suggest they enhance the outcome. Patient selection remains an important issue in this patient population. Individuals who are asymptomatic and have limited pulmonary or soft-tissue disease are most likely to benefit. The roles of immune dysregulation and the addition of novel cytostatic agents to these regimens are under investigation.

19
UI - 21253721
AU - Pantuck AJ; Zisman A; Belldegrun A
TI - Biology of renal cell carcinoma: changing concepts in classification and staging.
SO - Semin Urol Oncol 2001 May;19(2):72-9
AD - Department of Urology, University of California School of Medicine, Los Angeles 90095-1738, USA.
Advances in our understanding of the pathogenesis, behavior, and importance of prognostic factors for renal cell carcinoma (RCC) have paved the way for increased sophistication in its classification and staging. In the past, lack of consistent classification and terminology for RCC histology and staging has complicated comparability of clinical studies looking at patient prognosis and response to treatment. In this review, the results of international consensus efforts to achieve uniform classification systems for RCC are outlined and some future directions are considered.

20
UI - 21253722
AU - Zhou M; Rubin MA
TI - Molecular markers for renal cell carcinoma: impact on diagnosis and treatment.
SO - Semin Urol Oncol 2001 May;19(2):80-7
AD - Department of Pathology, University of Michigan Medical School, Ann Arbor, USA.
Molecular tumor markers are used to aid the differential diagnosis of renal cell carcinoma and to monitor disease progression and recurrence. They may also provide prognostic information and help in the design of therapeutic regimens. So far, no satisfactory markers are available for the diagnosis of renal cell carcinoma. Many markers have been evaluated for their potential use as prognostic factors. Some are promising, yet need vigorous clinical trials to validate. Genetic changes detected by molecular and cytogenetic methods provide markers specific for renal cell carcinoma. High-throughput DNA and tissue microarray techniques promise to revolutionize the discovery and validation of novel molecular markers.

21
UI - 21253723
AU - Quek ML; Stein JP; Skinner DG
TI - Surgical approaches to venous tumor thrombus.
SO - Semin Urol Oncol 2001 May;19(2):88-97
AD - University of Southern California, Norris Comprehensive Cancer Center, Department of Urology, Los Angeles 90033, USA.
The extension of tumor thrombus into the vena cava by renal cell carcinoma remains a technically challenging surgical condition. Attention to surgical detail and perioperative care can provide long-term survival in the appropriately selected patient. In reviewing our experience of 99 patients with venous tumor extension: renal vein only (n = 31), infrahepatic vena cava (n = 22), intrahepatic vena cava (n = 34), and intra-atrial extension (n = 12), we have demonstrated overall 2- and 5-year survival rates of 54% and 33%, respectively. Level of tumor thrombus appears to be correlated with overall survival. We continue to advocate an aggressive, optimistic approach for those patients with clinically confined tumors with isolated venous tumor thrombus extension.

22
UI - 21253724
AU - Flanigan RC; Yonover PM
TI - The role of radical nephrectomy in metastatic renal cell carcinoma.
SO - Semin Urol Oncol 2001 May;19(2):98-102
AD - Department of Urology, Loyola University Medical Center, Maywood, IL 60153-5500, USA.
The role of cytoreductive surgery in patients with metastatic renal cancer remains controversial. Recent data from our Southwest Oncology Group trial suggest that cytoreduction confers an approximately 50% increase in median survival for such patients when they are treated with interferon-alfa-2b immunotherapy. The timing of cytoreduction, and in which patients it may be most applicable, are discussed herein.

23
UI - 21409373
AU - Mizoguchi H; Yano A; Hashimoto K; Ohkuchi T; Emoto A; Ohno H; Nasu N
TI - [Laparoscopy-assisted total nephroureterectomy for renal pelvic and/or lower ureteral cancer]
SO - Nippon Hinyokika Gakkai Zasshi 2001 Jul;92(5):554-9
AD - Department of Urology, Nakatsu Daiichi Hospital, Nakatsu, Japan.
PURPOSE: The usefulness of laparoscopy-assisted total nephroureterectomy for patients with renal pelvic and lower ureteral cancer is evaluated. MATERIAL: Seven patients with renal pelvic cancer and four with lower ureteral cancer performed laparoscopy-assisted total nephroureterectomy from May 1997 to December 2000 (Ten males and one female, mean age 68.5 year-old). METHOD: Of the 11 patients, the initial one received preoperative embolization of the renal artery. Under general anesthesia laparoscopy-assisted total nephroureterectomy underwent via transperitoneal approach in three patients and retroperitoneal approach in eight. After the kidney was completely dissected under laparoscopic procedure, it was delivered en bloc with ureter from the skin incision in the lower abdomen. RESULT: Two patients needed conversion to open surgery. The mean operating time of nine patients except for conversion cases was 272 minutes and the mean blood loss was 313 ml. There was no major complication associated with laparoscopic procedure. There was no significant difference in both complication and recurrence rate between laparoscopy-assisted total nephroureterectomy and open surgery. CONCLUSION: Laparoscopy-assisted total nephroureterectomy is an useful procedure for the treatment of patients with renal pelvic and lower ureteral cancer because it enables us to remove out the kidney and ureter from one small lower abdominal incision.

24
UI - 21396556
AU - Takahashi M; Rhodes DR; Furge KA; Kanayama H; Kagawa S; Haab BB; Teh BT
TI - Gene expression profiling of clear cell renal cell carcinoma: gene identification and prognostic classification.
SO - Proc Natl Acad Sci U S A 2001 Aug 14;98(17):9754-9
AD - Laboratories of Cancer Genetics, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
To better understand the molecular mechanisms that underlie the tumorigenesis and progression of clear cell renal cell carcinoma (ccRCC), we studied the gene expression profiles of 29 ccRCC tumors obtained from patients with diverse clinical outcomes by using 21,632 cDNA microarrays. We identified gene expression alterations that were both common to most of the ccRCC studied and unique to clinical subsets. There was a significant distinction in gene expression profile between patients with a relatively nonaggressive form of the disease [100% survival after 5 years with the majority (15/17 or 88%) having no clinical evidence of metastasis] versus patients with a relatively aggressive form of the disease (average survival time 25.4 months with a 0% 5-year survival rate). Approximately 40 genes most accurately make this distinction, some of which have previously been implicated in tumorigenesis and metastasis. To test the robustness and potential clinical usefulness of this molecular distinction, we simulated its use as a prognostic tool in the clinical setting. In 96% of the ccRCC cases tested, the prediction was compatible with the clinical outcome, exceeding the accuracy of prediction by staging. These results suggest that two molecularly distinct forms of ccRCC exist and that the integration of expression profile data with clinical parameters could serve to enhance the diagnosis and prognosis of ccRCC. Moreover, the identified genes provide insight into the molecular mechanisms of aggressive ccRCC and suggest intervention strategies.

25
UI - 21417679
AU - Khoo SK; Bradley M; Wong FK; Hedblad MA; Nordenskjold M; Teh BT
TI - Birt-Hogg-Dube syndrome: mapping of a novel hereditary neoplasia gene to chromosome 17p12-q11.2.
SO - Oncogene 2001 Aug 23;20(37):5239-42
AD - Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
Birt-Hogg-Dube syndrome (BHD) is an autosomal dominant neoplasia syndrome characterized mainly by benign skin tumors, and to a lesser extent, renal tumors and spontaneous pneumothorax. To map the BHD locus, we performed a genome-wide linkage analysis using polymorphic microsatellite markers on a large Swedish BHD family. Evidence of linkage was identified on chromosome 17p12-q11.2, with a maximum LOD score of 3.58 for marker D17S1852. Further haplotype analysis defined a approximately 35 cM candidate interval between the two flanking markers, D17S1791 and D17S798. This information will facilitate the identification of the BHD gene, leading to the understanding of its underlying molecular etiology.

26
UI - 21407495
AU - Scatarige JC; Sheth S; Corl FM; Fishman EK
TI - Patterns of recurrence in renal cell carcinoma: manifestations on helical CT.
SO - AJR Am J Roentgenol 2001 Sep;177(3):653-8
AD - Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins Hospital, Baltimore, MD 21287, USA.

27
UI - 21433633
AU - Kankuri M; Pelliniemi TT; Pyrhonen S; Nikkanen V; Helenius H; Salminen E
TI - Feasibility of prolonged use of interferon-alpha in metastatic kidney carcinoma: a phase II study.
SO - Cancer 2001 Aug 15;92(4):761-7
AD - Department of Oncology and Radiotherapy, Turku University Hospital, Kiinamyllynkatu 4-8, FIN-20520 Turku, Finland. Minna.Kankuri@utu.fi
BACKGROUND: Interferon-alpha has proven effective in the treatment of metastatic renal cell carcinoma. However, the optimal schedule has not yet been determined. The authors have studied the efficacy and toxicity of prolonged use interferon-alpha2a (IFN-alpha) in metastatic renal cell carcinoma (RCC). Interferon-alpha was administered intermittently for outpatients. METHODS: Seventy-five patients with metastatic RCC without prior biochemotherapy were treated. During the first month, the IFN-alpha dose was increased from 4.5 to 18 million units (MU) 3 times a week to define the individual maximal tolerated dose for each patient. The treatment was continued at the maximal tolerated dose with a 1-week pause each month until either progression or intolerable toxicity was observed or up to 2 years. RESULTS: The overall response rate (5 complete response [CRs] and 8 partial responses [PRs]) was 17% (95% confidence interval, 10-28%). Stable disease was observed in 32 patients (43%). Three late objective responses (4%) occurred after 12 months treatment. The median progression free time of all patients was 12.3 months, and median survival time was 19.3 months. The median duration of response in CR/PR patients was 16 months. In multivariate analysis independent prognostic factors were poor performance status (P = 0.004), presence of bone metastases (P = 0.001), and time to metastases less than 24 months (P = 0.003), which predicted poor survival. Six patients (8%) discontinued the treatment because of fatigue, elevation of liver enzymes, or cardiac arrhythmias. No life-threatening side effects were observed. CONCLUSIONS: Prolonged and intermittently administered IFN-alpha2a three times per week in 3 weekly cycles in metastatic RCC is a feasible and effective therapy. A prolonged treatment duration of more than 12 months for stable and responding patients is beneficial and may improve the outcome of patients with RCC. Copyright 2001 American Cancer Society.

28
UI - 21397890
AU - Cho M; Uemura H; Kim SC; Kawada Y; Yoshida K; Hirao Y; Konishi N; Saga S; Yoshikawa K
TI - Hypomethylation of the MN/CA9 promoter and upregulated MN/CA9 expression in human renal cell carcinoma.
SO - Br J Cancer 2001 Aug 17;85(4):563-7
AD - Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
MN/CA9 is a cancer-related gene, frequently activated in human renal cell carcinomas (RCCs). To reveal the activation mechanism, we investigated the relationship between methylation status of the MN/CA9 promoter region and gene expression using 13 human RCCs, and examined the effect of in vitro CpG methylation on the MN/CA9 promoter activity using a human RCC cell line (SK-RC-44), expressing MN/CA9. MN/CA9 expression was evaluated by RT-PCR and observed in 10 of 13 RCCs (77%). A total of 9 out of 10 MN/CA9 -positive RCCs (90%) contained clear cell components. Methylation status of 6 CpGs in the MN/CA9 promoter region was decided by using the bisulfite genomic sequencing protocol. Out of 13 RCCs 9 (69%) showed partial hypomethylation of the CpG at -74 bp, while the other 4 RCCs and 3 normal kidney tissue samples showed complete methylation. Hypomethylation of the CpG at -74 bp was strongly correlated with MN/CA9 expression. Luciferase assay revealed that the MN/CA9 promoter activity was strongly suppressed by methylation of the CpG at -74 bp. These findings suggest that hypomethylation of the CpG at -74 bp in the MN/CA9 promoter region might play an important role in this gene activation of human RCC. Copyright 2001 Cancer Research Campaign.

29
UI - 21424073
AU - Zisman A; Pantuck AJ; Figlin RA; Belldegrun AS
TI - Validation of the ucla integrated staging system for patients with renal cell carcinoma.
SO - J Clin Oncol 2001 Sep 1;19(17):3792-3

30
UI - 21402853
AU - Bernauer TA; Mirowski GW; Caldemeyer KS
TI - Tuberous sclerosis. Part II. Musculoskeletal and visceral findings.
SO - J Am Acad Dermatol 2001 Sep;45(3):450-2
AD - Department of Radiology, Division of Neuroradiology, Indiana University Medical Center, 550 N University Blvd., Indianapolis, IN 46202, USA.

31
UI - 21395920
AU - Vaishampayan U; Flaherty L; Du W; Hussain M
TI - Phase II evaluation of paclitaxel, alpha-interferon, and cis-retinoic acid in advanced renal cell carcinoma.
SO - Cancer 2001 Aug 1;92(3):519-23
AD - Division of Hematology/Oncology, Department of Medicine, Wayne State University School of Medicine/Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA. vaishamu@karmanos.org
BACKGROUND: Interferon and 13-cis-retinoic acid (13-CRA) therapy showed clinical response rates of 30% in advanced renal cell carcinoma (RCC). This combination also enhanced sensitivity to paclitaxel in a bcl-2 and mutant p53 expressing renal carcinoma cell line. Based on this, the authors conducted a Phase II clinical trial of the combination of interferon, 13-CRA, and weekly paclitaxel, in advanced RCC. METHODS: The eligibility criteria consisted of unresectable or metastatic RCC, measurable disease, a Southwest Oncology Group performance status of 0-2, and adequate bone marrow, hepatic, and renal function. Prior cytotoxic or immunologic treatment including interferon was permitted. Paclitaxel was administered at a dose of 80 mg/m(2) as a 1-hour intravenous infusion on Days 1, 8, and 15 of each 28-day cycle. Interferon was administered at a dose of 3 million units subcutaneously daily and 13-CRA at 1 mg/kg/day orally in 2 divided doses for the first 21 days of each cycle. RESULTS: Twenty-one patients were enrolled with a median age of 52 years, 16 males and 5 females, 10 patients with no prior therapy, 5 each with prior interleukin-2 or interferon therapy, and 1 patient with both. Four patients had also received prior investigational chemotherapy. A total of 61 cycles were administered with a median of 2 per patient. Grade 3 and 4 toxicities were neutropenia in three patients, anemia in four patients, and asthenia, skin rash, and hypersensitivity reaction in one case each. Of the 20 evaluable patients, one objective partial response was observed for a duration of 7+ months. Seven patients had disease stabilization. The median survival of the entire population was 9.5 months (range, 4-18+ months). CONCLUSIONS: The combination of 13-CRA, interferon, and weekly paclitaxel was well tolerated and had minimal efficacy in advanced RCC. Copyright 2001 American Cancer Society.

32
UI - 20529556
AU - Siow WY; Yip SK; Ng LG; Tan PH; Cheng WS; Foo KT
TI - Renal cell carcinoma: incidental detection and pathological staging.
SO - J R Coll Surg Edinb 2000 Oct;45(5):291-5
AD - Department of Urology, Singapore General Hospital, Singapore.
In developed countries, there has been increased incidental detection of renal cell carcinoma (RCC). The incidence, pathological stage and survival of incidentally detected carcinoma in a developing country in Asia where, from 1990 to 1998, 165 renal cell carcinomas were identified. The clinical presentation, diagnostic-imaging modality employed, pathological staging and patient survival was reviewed. Incidental renal cancers included those that were diagnosed through health screening or detected incidentally through imaging studies for other conditions. The survival between these incidentally detected lesions and their symptomatic counterparts (suspected group) was compared. Sixty-four patients (39%) had their tumours detected incidentally, including 39 who were entirely asymptomatic and 25 who presented with non-specific symptoms, not initially suggestive of RCC. For the entire group, computed tomography provided the definitive diagnosis in 81% of cases. The incidental detection group had significantly smaller size of tumour (5.9 cm c.f. 7.6 cm), lower stage and lower histological grading. In particular, 78% of patients with incidental RCC had stage I or II diseases (TNM stage classification), compared with 57% of patients with suspected tumour (p < 0.05; Chi-square test). The disease free survival was significantly better for those with incidental detection (86% c.f. 66% at last follow up; p < 0.05; log-rank test) over a mean follow up period of 33 months (range 1-91). Regression analysis showed that stage of disease was the only independent variable predictive of clinical outcome. In conclusion, that significant numbers of RCC were detected incidentally. These tumours were of a lower clinical pathological stage and had a better prognosis.

33
UI - 21133351
AU - Lane T
TI - Renal cell carcinoma: incidental detection and pathological staging. 2000; 45(5):291-295.
SO - J R Coll Surg Edinb 2001 Feb;46(1):69

34
UI - 21217013
AU - Steiner T; Junker U; Salamon A; Nuske K; Schubert J
TI - Differential expression of cytokines and cytokine receptors in renal cell carcinoma.
SO - Urol Int 2001;66(3):140-4
AD - Department of Urology, Friedrich Schiller University, Jena, Germany. thomas.steiner@med.uni-jena.de
Modulation of immunomechanisms by tumor cells can be caused by secretion of cytokines. In vitro data are usually gained in culture systems. It is debatable whether these systems are representative of the conditions inside the respective tumor tissues. Immunohistochemical studies of