• Differential gene expression in renal-cell cancer.

• Impact of surgery on survival in palliative patients with metastatic colorectal cancer after first line treatment with weekly 24-hour

• Evaluation of sonographically guided percutaneous core biopsy of renal masses.

• Update on pathologic staging of renal cell carcinoma.

• Renal cell carcinoma-associated G250 methylation and expression: in vivo and in vitro studies.

• Minichromosome maintenance protein 2 expression in normal kidney and renal cell carcinomas: relationship to tumor dormancy and potential

• Renal cell carcinoma and occupational exposure to chemicals in Canada.

• [Studies on the interaction between interleukin-6 and human renal cell carcinoma cell line GRC-1]

• Quantitative analysis of gene expressions of vascular endothelial growth factor-related factors and their receptors in renal cell carcinoma.

• Functional and gene expression analysis of the p53 signaling pathway in clear cell sarcoma of the kidney and congenital mesoblastic nephroma.

• VEGF165b, an inhibitory splice variant of vascular endothelial growth factor, is down-regulated in renal cell carcinoma.

• Mutations in OGG1, a gene involved in the repair of oxidative DNA damage, are found in human lung and kidney tumours.

• Alterations of the DNA repair gene OGG1 in human clear cell carcinomas of the kidney.

• hOGG1 gene alterations in human clear cell carcinomas of the kidney: effect of single mutations in hOGG1 gene on substrate specificity of the

• Renal cell carcinoma related novel gene, GYLZ-RCC18: cloning and functional studies.

• Numerical chromosomal aberrations in papillary renal cortical tumors: relationship with histopathologic features.

• Renal cell carcinoma in the solitary kidney: an analysis of complications and outcome after nephron sparing surgery.

• Primary apoptosis as a prognostic index for the classification of metastatic renal cell carcinoma.

• Re: Percutaneous radio frequency ablation of small renal tumors: initial results.

• Activation of signal transducer and activator of transcription 3 in renal cell carcinoma: a study of incidence and its association with

• [Laparoscopic tumor nephrectomy]

• [Long-term results of organ-preserving surgeries for renal cell carcinoma]

• Cryptic t(12;15)(p13;q26) producing the ETV6-NTRK3 fusion gene and no loss of IGF2 imprinting in congenital mesoblastic nephroma with trisomy

• Clinical significance of allelic loss of chromosome region 5q22.3 approximately q23.2 in nonpapillary renal cell carcinoma.

• Bladder neoplasms after nephroureterectomy: does the surgery of the lower ureter, transurethral resection or open surgery, influence the

• Disruption of a novel MFS transporter gene, DIRC2, by a familial renal cell carcinoma-associated t(2;3)(q35;q21).

• [Multi-slice CT in the planning of nephron-sparing interventions for renal cell carcinoma: Prospective study correlated with histopathology]

• Between the Scylla and Charybdis of peptide radionuclide therapy: hitting the tumor and saving the kidney.

• 131 I-cG250 monoclonal antibody immunoscintigraphy versus [18 F]FDG-PET imaging in patients with metastatic renal cell carcinoma: a comparative

• Prognostic value of nuclear grading in patients with intracapsular (pT1-pT2) renal cell carcinoma. Long-term analysis in 213 patients.

• A phase II trial of intravenous gemcitabine and 5-fluorouracil with subcutaneous interleukin-2 and interferon-alpha in patients with

• Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma.

• Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based

1
UI - 12080328
AU - Skubitz KM; Skubitz AP
TI - Differential gene expression in renal-cell cancer.
SO - J Lab Clin Med 2002 Jul;140(1):52-64
AD - Department of Medicine, University of Minnesota Medical School, Minneapolis, USA.
Renal-cell carcinoma (RCC) is an important cause of morbidity and mortality, and its incidence has been increasing. Malignant transformation is thought to be associated with changes in the expression of several genes, and this alteration in gene expression is believed to be critical to the development of the malignant phenotype. In this study, the expression of about 60,000 genes/expressed sequence tags in clear-cell RCC, normal kidney, and a set of diseased nonmalignant kidneys was determined with the use of the Affymetrix microarray technique, and differences in gene expression were analyzed. Many genes were found to be differentially expressed in these two sample sets. The genes that were expressed greater than four times more in RCC, those expressed only in RCC, and those expressed greater than two times more in RCC and also expressed in a limited number of other tissues were analyzed for their expression in a variety of other normal and diseased tissues. Some of the genes identified were overexpressed only in RCC among the tissues examined, and some were overexpressed in several other malignant tissues in addition to RCC. Other genes were overexpressed in RCC compared with normal kidney but were also overexpressed in diseased nonmalignant kidney or a variety of other normal tissues. All of the RCC samples could be clustered together, separate from the normal and diseased kidney samples, with the use of the Eisen clustering technique and a set of 50 genes. The observed changes in gene expression in RCC should help further the understanding of the biology of RCC and may be useful in diagnosis, treatment, and imaging.

2
UI - 11843250
AU - Wein A; Riedel C; Kockerling F; Martus P; Baum U; Brueckl WM; Reck T;
TI - Ott R; Hansler J; Bernatik T; Becker D; Schneider T; Hohenberger W; Hahn EG Impact of surgery on survival in palliative patients with metastatic colorectal cancer after first line treatment with weekly 24-hour infusion of high-dose 5-fluorouracil and folinic acid.
SO - Ann Oncol 2001 Dec;12(12):1721-7
AD - Department of Internal Medicine I, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany. Axel.Wein@med1.imed.uni-erlangen.de
BACKGROUND: In palliative first-line treatment of colorectal cancer, the secondary resection of distant metastases after downstaging has constantly gained in importance. The objective of this prospective study was to examine the tumor response rate, the toxicity, the median survival time and the prognostic impact of metastatic resection after downstaging of consecutively enrolled patients with primary nonresectable colorectal cancer treated with once weekly 24-hour (24-h) infusion of high-dose 5-fluorouracil (5-FU) and folinic acid. PATIENTS with primary nonresectable metastases were recruited for a prospective phase II study. The patients received in out-patient care 500 mg/m2 folinic acid in the form of a 1-2-hour infusion followed by 2600 mg/m2 5-FU administered as a 24-h infusion once weekly. One treatment cycle comprised six weekly infusions followed by a two week rest. Three cycles were administered, and in the event of complete remission (CR) or partial remission (PR) and good tolerability, a fourth cycle was undertaken. Thereafter, the possibility of performing a curative metastatic resection was investigated. RESULTS: Of the 53 patients treated, 7 showed a CR (13%), 15 patients a PR (28%), 26 patients stable disease (SD) (49%), and 5 patients progressive disease (PD) (10%). As the main symptom of toxicity, diarrhea (CTC grade 3 + 4) was observed in 11 patients (21%), followed by leucocytopenia (CTC grade 3 + 4) in 2 patients (4%), and the hand-foot syndrome in 1 patient (2%). The median survival time was 17 months with a median follow-up of 41 months (range: 28-59 months). In 9 patients (17%), a secondary metastatic resection was considered; in 6 patients (11%) curative resection was performed, and 4 patients (8%) showed no evidence of disease for at least three years. CONCLUSION: In this phase II study, we have been able to show prospectively that, after downstaging by palliative treatment using a weekly 24-h infusion of high-dose 5-FU and folinic acid, secondary curative metastatic resection was technically feasible in 11% of the patients. For some of these patients, long-term survival is therefore possible. Secondary metastatic resection should be carried out in close interdisciplinary cooperation, and should be further investigated in prospective phase III studies.

3
UI - 12130435
AU - Caoili EM; Bude RO; Higgins EJ; Hoff DL; Nghiem HV
TI - Evaluation of sonographically guided percutaneous core biopsy of renal masses.
SO - AJR Am J Roentgenol 2002 Aug;179(2):373-8
AD - Department of Radiology, University of Michigan Medical Center, 1500 E. Medical Center Dr., Taubman Center 2910R, Ann Arbor, MI 48109-9723, USA.
OBJECTIVE: Our objective was to determine the utility of sonographically guided percutaneous core biopsy to evaluate renal masses. MATERIALS AND METHODS: We conducted a retrospective analysis of our imaging-guided sonographically guided percutaneous core biopsies of renal masses in 26 patients. From two to five specimens were obtained from a single mass in each patient using an 18-gauge automated biopsy system. We examined the patients' medical records, pathology results, and imaging studies. Core biopsy results were compared with surgical pathology (n = 6) or clinical follow-up (n = 20). RESULTS: All biopsies provided sufficient material for analysis. Biopsy findings were positive for malignancy in 19 (73%) of 26 masses. Histologic diagnoses included renal cell carcinoma were (n = 11), metastasis (n = 3), lymphoma (n = 2), and transitional cell carcinoma (n = 2). Specific cell type characterization could not be made on one biopsy, but the specimens were highly suspicious for malignancy. Biopsy revealed seven (27%) of 26 benign diagnoses: oncocytoma (n = 3), angiomyolipoma (n = 2), and fibrosis (n = 2). The average follow-up period for patients with benign diagnoses was 10 months. One case of surgically proven necrotic pyelonephritis was mischaracterized as fibrosis at core biopsy. Sonographically guided percutaneous core biopsy of renal masses showed a sensitivity of 100% and a specificity of 100% for the diagnosis of malignancy. The core specimens yielded a specific diagnosis in 92% (24/26) of masses. No immediate complications occurred after the procedure. One patient developed a pseudoaneurysm that presented 3 months after the biopsy. CONCLUSION. Sonographically guided percutaneous core biopsy is a reliable and accurate method for evaluating renal masses.

4
UI - 12137811
AU - Gettman MT; Blute ML
TI - Update on pathologic staging of renal cell carcinoma.
SO - Urology 2002 Aug;60(2):209-17
AD - Department of Urology, Mayo Clinic, Rochester, Minnesota 55905, USA.

5
UI - 12137853
AU - Grabmaier K; de Weijert M; Uemura H; Schalken J; Oosterwijk E
TI - Renal cell carcinoma-associated G250 methylation and expression: in vivo and in vitro studies.
SO - Urology 2002 Aug;60(2):357-62
AD - Experimental Urology, Department of Urology, University Medical Center Nijmegen, Nijmegen, The Netherlands.
OBJECTIVES: In renal cell carcinoma (RCC) cell lines, expression of the RCC-associated antigen G250 correlates with hypomethylation of the investigated CpG dinucleotides in the G250 promoter region, despite the absence of a CpG island. To gain insight into the molecular mechanism leading to G250 expression in vivo, we ascertained whether this correlation between G250 gene expression and the methylation status of the G250 gene also existed in primary RCC and normal kidney tissue. METHODS: G250 mRNA and protein expression was determined by reverse transcriptase-polymerase chain reaction, fluorescence activated cell sorting analysis, and immunohistochemistry in 15 RCC cell lines and 13 paired primary RCC/normal kidney tissue specimens. The methylation status of the G250 gene was determined by bisulfite genomic sequencing. RESULTS: RCC cell lines revealed a clear correlation between G250 expression and hypomethylation. In contrast, no hypomethylation was observed in primary RCC compared with normal kidney tissue. The CpG dinucleotides investigated were generally completely methylated in RCC, as well as in normal kidney tissue. Furthermore, a primary culture of RCC tissue revealed increasing hypomethylation of the G250 gene in successive passages, suggesting that the G250 hypomethylation observed in vitro is tissue culture induced. CONCLUSIONS: The methylation status of the G250 gene correlated with G250 expression in vitro but not in vivo.

6
UI - 11948116
AU - Rodins K; Cheale M; Coleman N; Fox SB
TI - Minichromosome maintenance protein 2 expression in normal kidney and renal cell carcinomas: relationship to tumor dormancy and potential clinical utility.
SO - Clin Cancer Res 2002 Apr;8(4):1075-81
AD - Anatomical Pathology, Canterbury Health Laboratories, Christchurch Hospital, Christchurch, New Zealand 8001.
PURPOSE: A major problem in the management of patients with renal cell carcinoma is predicting tumor behavior. In the search for more accurate markers of prognosis, tumor cell proliferation has been investigated. These studies have mostly used antibodies directed against Ki-67 or proliferating cell nuclear antigen and have given conflicting results, findings that are likely because of a combination of specificity and methodological differences. Minichromosome maintenance (Mcm) proteins are a series of closely related proteins that are components of the prereplicative complex. The Mcm proteins are essential for initiating eukaryotic DNA replication and serve as useful markers of proliferating cells. EXPERIMENTAL DESIGN: The aims of this study were to determine the frequency and pattern of Mcm2 expression by immunohistochemistry in normal kidney (n = 10) and renal tumors [n = 56; clear cell n = 36; chromophil (papillary) n = 7; oncocytoma n = 5; and transitional cell carcinoma n = 8], compare its sensitivity to the established proliferation marker Ki-67, examine for differences in tumors derived from stable and labile epithelial cell populations in the kidney, and assess the relationship of Mcm2 proliferation to clinicopathological characteristics of kidney tumors. In addition, to additionally investigate the issue of tumor dormancy we wished to assess the relationship between Mcm2 labeling index (LI) and the angiogenic factors angiopoietin-1 (Ang) and Ang-2. RESULTS: In normal tissues, Mcm2 nuclear labeling was identified in both glomeruli (LI median 0.35%; range 0-1.7) and renal tubules (LI median 0.3%; range 0.1-2.9%). In tumors Mcm2 labeling was predominantly at the periphery with LIs ranging from 0.2-91.5%, which was significantly greater than Ki-67 LI (0.2-40.5%; P < 0.001). Mcm2 LI was also significantly higher in tumors derived from a labile epithelium (transitional cell carcinomas) than a stable epithelium (renal cell carcinomas; P = 0.013). A significant association was also demonstrated between Mcm2 LI and tumor grade (P = 0.0006), and angiogenic phenotype (defined by Ang expression; P = 0.03) but not with patient age (P = 0.84), patient sex (P = 0.25), tumor size (P = 0.74), or stage (P = 0.33). Furthermore, although not significant, a survival analysis demonstrated that 100% of patients with a low Mcm2 LI survived compared with 84% of those with a high Mcm2 LI over the follow-up period (up to 53.2 months; P = 0.14). CONCLUSIONS: This is the first study examining Mcm2 protein in normal and tumor kidney samples, and the first to perform histological subgroup analysis. It shows that Mcm2 is a superior marker to Ki-67 in the assessment of cell cycle entry in histological archival material and that normal kidney has a subset of cells within the glomerular and tubular compartments that are in cycle. It demonstrates that the frequency of cells in cycle in tumors formed from stable or labile epithelial populations mirrors that in the nonneoplastic epithelium. This study additionally demonstrates that the number of cells in cycle in tumors is limited by the angiogenic phenotype and supports animal models that show angiogenesis determines the likelihood of tumor dormancy. Additional study to confirm the clinical utility of Mcm2 as a prognostic marker is now indicated.

7
UI - 12063361
AU - Hu J; Mao Y; White K
TI - Renal cell carcinoma and occupational exposure to chemicals in Canada.
SO - Occup Med (Lond) 2002 May;52(3):157-64
AD - Surveillance & Risk Assessment, Centre for Chronic Disease Prevention and Control, Population and Public Health Branch, Health Canada, Ottawa, Ontario, Canada..
This study assesses the effect of occupational exposure to specific chemicals on the risk of renal cell carcinoma in Canada. Mailed questionnaires were used to obtain data on 1279 (691 male and 588 female) newly diagnosed, histologically confirmed renal cell carcinoma cases and 5370 population controls in eight Canadian provinces, between 1994 and 1997. Data were collected on socio-economic status, smoking habit, alcohol use, diet, residential and occupational histories, and years of exposure to any of 17 chemicals. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived using unconditional logistic regression. The study found an increased risk of renal cell carcinoma in males only, which was associated with occupational exposure to benzene; benzidine; coal tar, soot, pitch, creosote or asphalt; herbicides; mineral, cutting or lubricating oil; mustard gas; pesticides; and vinyl chloride. Compared with no exposure to the specific chemical, the adjusted ORs were 1.8 (95% CI = 1.2-2.6), 2.1 (1.3-3.6), 1.4 (1.1-1.8), 1.6 (1.3-2.0), 1.3 (1.1-1.7), 4.6 (1.7-12.5), 1.8 (1.4-2.3) and 2.0 (1.2-3.3), respectively; an elevated risk was also associated with exposure to cadmium salts and isopropyl oil. The risk of renal cell carcinoma increased with duration of exposure to benzene, benzidine, cadmium, herbicides and vinyl chloride. Very few females were exposed to specific chemicals in this study; further research is needed to clarify the association between occupational exposure to chemicals and renal cell carcinoma in females.

8
UI - 11798778
AU - Xi Z; Yu L; Guo Y
TI - [Studies on the interaction between interleukin-6 and human renal cell carcinoma cell line GRC-1]
SO - Zhonghua Yi Xue Za Zhi 2000 Apr;80(4):308-11
AD - Institute of Urology, The 1st Hospital of Beijing Medical University, Beijing 100034, China.
OBJECTIVE: To demonstrate the effects of IL-6 on the renal cell carcinoma cell line GRC-1. METHODS AND RESULTS: Immunocytochemical staining and RT-PCR analysis indicated that this cell line could express IL-6 both on mRNA and protein levels. Secretion of IL-6 in this cell line was 465 pg/ml, which was identified by ELISA assay. By RT-PCR analysis, we found that GRC-1 expressed IL-6 receptor system including IL-6 mRNA and gp130 mRNA. The rhIL-6 did not stimulate the growth of GRC-1 while the neutralizing antibody did not inhibit its growth. For further identification of the effect of IL-6 on GRC-1 cells, we introduced an antisense IL-6 RNA into GRC-1 cells. Thereafter, the lowered expression of IL-6 mRNA was observed by Northern blot, and the secretion of IL-6 was reduced to 250 pg/ml. But there were no significant growth-inhibitory effects on GRC-1 cells. CONCLUSION: Although GRC-1 could express IL-6, IL-6 R and gp130, the rhIL-6 and IL-6 neutralizing antibody or transducing antisense IL-6 RNA could not change the growth of GRC-1 cells significantly. These results suggest that it is not likely for IL-6 functioning as an autocrine growth factor for GRC-1.

9
UI - 11846206
AU - Tsuchiya N; Sato K; Akao T; Kakinuma H; Sasaki R; Shimoda N; Satoh S;
TI - Habuchi T; Ogawa O; Kato T Quantitative analysis of gene expressions of vascular endothelial growth factor-related factors and their receptors in renal cell carcinoma.
SO - Tohoku J Exp Med 2001 Oct;195(2):101-13
AD - Department of Urology, Akita University School of Medicine, Japan.
Vascular endothelial growth factor (VEGF)-related factors are believed to regulate angiogenesis, an essential event in the growth of solid tumors. In this study, we investigated the expression of VEGF-related factor genes (VEGF, VEGF-B, and VEGF-C) and their receptor genes (VEGFR-1 and VEGFR-2) in renal cell carcinoma (RCC). There were significant differences in the expression level of VEGF, VEGFR-1 and VEGFR-2 between RCC and the corresponding normal renal tissue. The expression level of VEGF in the tumor tissue significantly correlated with those of VEGFR-1 and VEGFR-2. Expression levels VEGF-B and VEGF-C genes were not significantly different between RCC and normal renal tissue. A moderate to high protein expression for VEGF, VEGFR-1, and VEGFR-2 was observed in both the tumor cells and the endothelial cells, whereas the protein expression was low for VEGF-B and VEGF-C. The present results suggested that VEGF and its receptors VEGFR-1 and VEGFR-2 cooperates to play a crucial role in the angiogenesis of RCC, while VEGF-B and VEGFR-C may not. Furthermore, since VEGFR-1 and VEGFR-2 proteins were expressed in the tumor cells as well as in the endothelial cells, these receptors may also be responsible for the progression of RCC.

10
UI - 12007018
AU - Brownlee NA; Hazen-Martin DJ; Garvin AJ; Re GG
TI - Functional and gene expression analysis of the p53 signaling pathway in clear cell sarcoma of the kidney and congenital mesoblastic nephroma.
SO - Pediatr Dev Pathol 2002 May-Jun;5(3):257-68
AD - Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425, USA.
Mutation of p53 has been implicated in progression of classical Wilms tumor (WT) into the anaplastic variant (AWT), drug resistance, and poor prognosis. Because of prognostic similarities, clear cell sarcoma of the kidney (CCSK) has been classified with AWT and other aggressive pediatric renal tumors, apart from congenital mesoblastic nephroma (CMN), which is instead a relatively benign tumor of neonates. Initially, CCSK and CMN were assumed to be ontologically related, but the role of p53 in the pathogenesis of either disease has not been sufficiently evaluated as in AWT. We examined the status of p53 in CMN and CCSK in comparison to AWT by immunohistochemistry and mRNA analysis of p53, the downstream effector p21(WAF-1/CIP-1) ( p21), the multidrug resistance gene MDR-1, a putative target of p53, and the p53-antagonist Mdm-2. Surprisingly, strong p53 nuclear immunoreactivity was found in cultures from two CMN specimens, but not in frozen or fixed tumor tissue from five other CMN specimens, nor in cell lines or tumor tissue from CCSK. Sequence analysis excluded p53 mutations. The size of the p53 mRNA in CMN and CCSK primary tumors excluded gross deletions or rearrangements. Low levels of Mdm-2 mRNA in CCSK and CMN primary tumors and cultures did not support a role for Mdm-2. Absence of MDR-1 mRNA excluded MDR-1 in the drug-resistant phenotype of CCSK. Cisplatin-induced p21 transactivation assays and G(1) cell cycle arrest analyses showed that p21 transactivation and G(1) arrest occurred in both CCSK and CMN cultures, demonstrating integrity of the p53 signal transduction pathway. Absence of p53 functional abnormalities excluded relationships between CCSK and CMN as in AWT, supporting the association of cellular CMN with congenital fibrosarcomas as more recently proposed.

11
UI - 12124351
AU - Bates DO; Cui TG; Doughty JM; Winkler M; Sugiono M; Shields JD; Peat D;
TI - Gillatt D; Harper SJ VEGF165b, an inhibitory splice variant of vascular endothelial growth factor, is down-regulated in renal cell carcinoma.
SO - Cancer Res 2002 Jul 15;62(14):4123-31
AD - Microvascular Research Laboratories, Department of Physiology, Preclinical Veterinary School, University of Bristol, Bristol BS2 8EJ, United Kingdom.
Angiogenesis is essential for tumor growth. Vascular endothelial growth factor (VEGF) is the most potent growth factor of tumor neovasculature, has been shown to be up-regulated in every tumor studied thus far, and is correlated with tumor stage and progression. To determine whether specific VEGF splice variants were differentially expressed in renal cell carcinomas, 18 polar tumor samples were analyzed by reverse transcription-PCR using primers designed to differentiate between VEGF splice variants. Control tissue was derived from the opposite normal pole. An amplicon of length consistent with the previously described variant VEGF(148) was found in normal kidney tissue. Subsequent sequencing revealed a new VEGF isoform formed by differential splicing from the end of exon 7 into the 3' untranslated region of the mRNA. Cloning of this transcript showed that translation would result in a 165-amino acid peptide with an alternative terminal 6 amino acids, followed by a stop codon. We have termed this new isoform VEGF165b. This isoform was present in 17 of 18 normal kidney samples but only 4 of 18 cases from matched malignant tissue. VEGF165b was therefore expressed in a significantly higher proportion of normal tissue than malignant tissue from the same patients (P < 0.001). To determine the functional significance of this new isoform, we expressed the full-length protein in a heterologous expression system. Conditioned medium containing this isoform significantly and dose dependently inhibited VEGF165-mediated proliferation, migration of endothelial cells, and vasodilatation of mesenteric arteries. This novel isoform VEGF165b is therefore an endogenous inhibitory form of VEGF that is down-regulated in renal tumors and, therefore, may be anti-angiogenesis.

12
UI - 9662341
AU - Chevillard S; Radicella JP; Levalois C; Lebeau J; Poupon MF; Oudard S;
TI - Dutrillaux B; Boiteux S Mutations in OGG1, a gene involved in the repair of oxidative DNA damage, are found in human lung and kidney tumours.
SO - Oncogene 1998 Jun 11;16(23):3083-6
AD - Departement de Radiobiologie et Radiopathologie, UMR217 CNRS-CEA Radiobiologie Moleculaire et Cellulaire, Fontenay aux Roses, France.
The human OGG1 gene encodes a DNA glycosylase activity catalysing the excision of the mutagenic lesion 7,8-dihydro-8-oxoguanine from oxidatively damaged DNA. The OGG1 gene was localized to chromosome 3p25, a region showing frequent loss of heterozygosity (LOH) in lung and kidney tumours. In this study, we have analysed by RT-PCR the expression of OGG1 in 25 small cell lung cancers, in 15 kidney carcinomas and the 15 normal kidney counterparts. The results show that OGG1 messenger RNA can be detected in all tumours tested and that no significant difference was observed in the level of expression between normal and tumoral kidney tissues. Denaturing gradient gel electrophoresis (DGGE) was used to screen this series of human tumours for alterations in the OGG1 cDNA. The study revealed homozygous mutations in three tumours, two from lung and one from kidney. Sequencing analysis of the mutants identified a single base substitution in each of the three cases: two transversions (GC to TA and TA to AT) and one transition (GC to AT). All three substitutions cause an amino acid change in the hOgg1 protein. For the mutant kidney tumour, the normal tissue counterpart shows a wild-type profile. These results suggest a role for OGG1 mutations in the course of the multistage process of carcinogenesis in lung or kidney.

13
UI - 10987279
AU - Audebert M; Chevillard S; Levalois C; Gyapay G; Vieillefond A;
TI - Klijanienko J; Vielh P; El Naggar AK; Oudard S; Boiteux S; Radicella JP Alterations of the DNA repair gene OGG1 in human clear cell carcinomas of the kidney.
SO - Cancer Res 2000 Sep 1;60(17):4740-4
AD - Commissariat a l'Energie Atomique, Departement de Radiobiologie et Radiopathologie, Fontenay aux Roses, France.
The OGG1 gene, which codes for a DNA repair protein with antimutator activity, is located on chromosome 3p25, a frequent site of allelic deletions in many types of human tumors, including renal clear cell cancers. We present the analysis of 99 renal tumors for alterations in the OGG1 gene to determine its association with tumorigenesis. Loss of heterozygosity in the 3p25 region was found for 85% of the informative cases. We detected somatic missense mutations of the OGG1 gene in 4 of the 99 tumor samples. Biochemical analysis of the mutant proteins revealed that a substitution at codon 46 impairs the enzymatic activity. We also describe the occurrence of several polymorphisms as well as aberrantly spliced OGG1 transcripts.

14
UI - 11765004
AU - Audebert M; Levalois C; Chevillard S; Dizdaroglu M; Boiteux S; Radicella
TI - JP hOGG1 gene alterations in human clear cell carcinomas of the kidney: effect of single mutations in hOGG1 gene on substrate specificity of the hOGG1 protein.
SO - Adv Exp Med Biol 2001;500():617-20
AD - CEA, UMR 217 CEA/CNRS, Departement de Radiobiologie et Radiopathologie, Fontenay-aux-Roses, France.

15
UI - 12133548
AU - Zhang Q; Chen L; Liang L; Xi Z; Ding Y; Tong M; Zhang Z; Lee C; Guo Y
TI - Renal cell carcinoma related novel gene, GYLZ-RCC18: cloning and functional studies.
SO - Chin Med J (Engl) 2002 May;115(5):746-9
AD - Department of Urology and Institute of Urology, The First Affiliated Hospital, Peking University, Beijing 100034, China. zhanqian@public3.bta.com
OBJECTIVE: To clone the full length of renal cell carcinoma (RCC) related novel gene GYLZ-RCC18 and study its function. METHODS: SMART RACE technology was used to clone the full length of GYLZ-RCC18. RT-PCR was used to detect its expression in renal cell carcinoma tissue at different stages and grades. We transfected the antisense oligonucleotide of GYLZ-RCC18 to renal cell carcinoma cell line, GRC-1, and analyzed proliferation activity, growth rate, apoptosis, and mortality changes. RESULTS: The full length of GYLZ-RCC18 (GenBank accession number: BE825133) cDNA was about 3.5 kb. GYLZ-RCC18 had a higher expression in higher grades and stages of renal cell carcinoma than in lower ones. The expression of GYLZ-RCC18 in renal cell carcinoma was much higher than in normal kidney. After the transfection of GYLZ-RCC18 antisense oligonucleotide, the mortality of GRC-1 increased significantly, while proliferative activity and growth rate were substantially inhibited at the same time. The antisense oligonucleotide induced apoptosis of GRC-1 through the entire observation time. CONCLUSION: GYLZ-RCC18 is an important novel gene related to renal cell carcinoma. Overexpression of this gene results in higher growth and proliferative activity and has an antiapoptosis effect on renal cell carcinoma cells. Transfection of the antisense oligonucleotide may inhibit the generation and development of renal cell carcinoma.

16
UI - 12070600
AU - Henke RP; Erbersdobler A
TI - Numerical chromosomal aberrations in papillary renal cortical tumors: relationship with histopathologic features.
SO - Virchows Arch 2002 Jun;440(6):604-9
AD - Institute of Pathology, Taubenstrasse 28, 26122 Oldenburg, Germany.
Previous studies have indicated that a combined trisomy of chromosomes 7 and 17 is a constant finding in papillary renal cortical adenomas and that papillary renal cell carcinomas are marked by additional trisomies such as trisomy 12, 16, and 20. The aim of our study was to compare this cytogenetic classification of papillary renal cortical tumors with conventional histopathologic classification. We performed interphase cytogenetics with enumeration probes for chromosomes 7, 12, 16, 17, and 20 on 41 papillary tumors found in 21 nephrectomy and 10 autopsy kidneys. A total of 38 tumors harbored gains of chromosomes 7 or 17, and most of these showed a trisomic signal distribution. The three tumors with normal copy numbers for chromosomes 7 and 17 were a papillary grade-2 carcinoma, a small adenoma (both with distinctive oxyphilic cytoplasm), and a papillary carcinoma with focally clear cells. Gains for chromosomes 12, 16, or 20 were found in 21 tumors and were significantly associated with the presence of histologic criteria of malignancy ( P<0.0001). Histopathologic and cytogenetic features of malignancy were found in eight tumors smaller than 10 mm. There is a good agreement of cytogenetic and histopathologic criteria of malignancy in papillary renal cell tumors. Interphase cytogenetics might give useful additional information in cases of doubt or when only small biopsy specimens are available.

17
UI - 12131287
AU - Ghavamian R; Cheville JC; Lohse CM; Weaver AL; Zincke H; Blute ML
TI - Renal cell carcinoma in the solitary kidney: an analysis of complications and outcome after nephron sparing surgery.
SO - J Urol 2002 Aug;168(2):454-9
AD - Department of Laboratory Medicine, Health Sciences Research and Urology, Mayo Clinic, Rochester, Minnesota, USA.
PURPOSE: We evaluated surgical techniques, pathological features and extended outcomes in patients with renal cell carcinoma in a solitary kidney treated with surgical excision. MATERIALS AND METHODS: Between 1970 and 1998, 76 patients underwent nephron sparing surgery for sporadic renal cell carcinoma in a solitary kidney, including 63 with tissue specimens available for pathological review who comprised the cohort. Six (9.5%) patients had a congenitally absent kidney and 57 (90.5%) had previously undergone contralateral nephrectomy for renal cell carcinoma. The clinical and pathological features examined were patient age at nephron sparing surgery, sex, type of nephron sparing surgery (enucleation, partial nephrectomy or ex vivo resection), tumor size, nuclear grade, histological subtype and 1997 tumor stage. Overall cancer specific, local recurrence-free and metastasis-free survival as well as early (within 30 days of nephron sparing surgery) and late (30 days to 1 year after nephron sparing surgery) complications were assessed. Univariate and multivariate analyses were done to test for the associations of clinical and pathological features with outcome. RESULTS: Most patients were treated with enucleation (36.5%), standard partial nephrectomy (38.1%) or the 2 procedures (11.1%) and in 8 (12.7%) ex vivo tumor resection was done. The renal cell carcinoma histological subtypes were clear cell in 82.5% of cases, papillary in 15.9% and chromophobe in 1.6%. Grade was 1 to 3 in 10 (15.9%), 42 (66.7%) and 10 (15.9%) tumors, respectively. At 5 and 10 years the overall survival rate was 74.7% and 45.8%, the cancer specific survival rate was 80.7% and 63.7%, the local recurrence-free survival rate was 89.2% and 80.3%, and the metastasis-free survival rate was 69% and 50.4%, respectively. Tumor stage and nuclear grade were significantly associated with death from any cause, death from renal cell carcinoma and distant metastases on multivariate analysis. Notably no patient with papillary or chromophobe renal cell carcinoma died of renal cell carcinoma, or had recurrence or metastasis. The type of nephron sparing surgery was not significantly associated with outcome, although there were too few patients with recurrence to assess the association of the type of nephron sparing surgery with local recurrence. The most common early complication was acute renal failure in 12.7% of cases, while the most common late complications were proteinuria in 15.9% and renal insufficiency in 12.7%. CONCLUSIONS: The 1997 tumor stage and nuclear grade were significant predictors of death from any cause, death from renal cell carcinoma and distant metastases in patients treated with nephron sparing surgery for renal cell carcinoma involving a solitary kidney. Nephron sparing surgery in a solitary kidney can be performed safely and with minimal morbidity.

18
UI - 12131288
AU - Richter EN; Oevermann K; Buentig N; Storkel S; Dallmann I; Atzpodien J
TI - Primary apoptosis as a prognostic index for the classification of metastatic renal cell carcinoma.
SO - J Urol 2002 Aug;168(2):460-4
AD - Hamatologie und Onkologie and Urologische Klinik, Medizinische Hochschule Hannover, Hannover, Germany.
PURPOSE: We identified novel biological markers of prognosis in primary histopathological specimens from patients with metastatic renal cell carcinoma. MATERIALS AND METHODS: Apoptotic indexes (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling), proliferation rates (Ki-67 antigen), p21 (WAF1/cip1) expression and CD95 (APO-1/Fas) expression were determined in paraffin embedded nephrectomy specimens from 73 patients with histologically confirmed, progressive metastatic disease. Kaplan-Meier survival analysis, log rank statistics and 2-proportional Cox regression analysis were done to identify new risk factors in addition to conventional classification criteria, and demonstrate statistical independence. RESULTS: Multivariate analysis indicated that primary tumor apoptosis (p = 0.0116) and the interval from diagnosis to metastatic disease (p = 0.002) had a high predictive impact on overall survival after initial diagnosis. Patients were assigned to 2 risk groups, namely a poor prognosis group with a median survival of 20 months, defined by apoptosis less than 6% in the primary tumor nephrectomy specimen and a time from initial diagnosis to metastatic disease of less than 6 months, and a good prognosis group with a median survival of 56 months, defined as the absence of 1 or 2 risk factors. CONCLUSIONS: Our findings showed that primary tumor apoptosis is a novel independent predictor in patients with metastatic renal cell carcinoma at initial diagnosis. It leads to a new prognostic index in the pretreatment classification of metastatic renal cell carcinoma.

19
UI - 12131338
AU - Ogan K; Cadeddu JA
TI - Re: Percutaneous radio frequency ablation of small renal tumors: initial results.
SO - J Urol 2002 Aug;168(2):660; discussion 660-1

20
UI - 12131365
AU - Horiguchi A; Oya M; Shimada T; Uchida A; Marumo K; Murai M
TI - Activation of signal transducer and activator of transcription 3 in renal cell carcinoma: a study of incidence and its association with pathological features and clinical outcome.
SO - J Urol 2002 Aug;168(2):762-5
AD - Department of Clinical Research and Urology, Saitama National Hospital and Department of Pathology, Saitama Medical School, Saitama, Japan.
PURPOSE: Signal transducer and activator of transcription 3 (STAT3) is known to have an important role in cytokine and growth factor signaling pathways. In various types of human malignant tumors STAT3 has been shown to be constitutively activated due to aberrant production of cytokines and growth factors. We examined the presence of STAT3 activation and its association with pathological features and clinical outcome in renal cell carcinoma cases. MATERIALS AND METHODS: We examined 48 paraffin embedded renal cell carcinoma specimens and corresponding nonneoplastic kidney tissues for the activation status of STAT3 on immunohistochemistry using anti-phospho-specific (p)-STAT3 antibody, which recognizes only activated STAT3. Based on the percent of cells with positive nuclear staining the activation status of STAT3 was determined and categorized into 2 groups, including low-less than 10% and high-90% or more tumor cells positive. The associations of the activation status of STAT3 with pathological features and clinical outcome were analyzed. RESULTS: Of 48 tumors 24 (50%) demonstrated high levels of nuclear immunostaining for p-STAT3, while the other 24 (50%) showed low levels. Adjacent nonneoplastic kidney tissues showed only little immunostaining for p-STAT3. A significant association of high levels of p-STAT3 with metastasis was observed (p = 0.0094). No significant associations of p-STAT3 immunostaining with pathological stage or grade were observed. A high level of p-STAT3 was a significant indicator of a poor prognosis on univariate and multivariate analysis (p = 0.0117 and 0.0439, respectively) CONCLUSIONS: Our results indicate a high frequency of STAT3 activation in renal cell carcinoma, especially in metastatic disease. STAT3 activation was an independent prognostic variable in renal cell carcinoma cases. Our results strongly suggest that the activation of STAT3 contributes to the development and progression of renal cell carcinoma.

21
UI - 11993086
AU - Janetschek G; al-Zachrani H; Vrabec G; Leeb K
TI - [Laparoscopic tumor nephrectomy]
SO - Urologe A 2002 Mar;41(2):101-6
AD - Abteilung fur Urologie, Krankenhaus der Elisabethinen, Fadingerstrasse 1, 4020 Linz/Osterreich. guenter.janetschek@elisabethinen.or.at
Initially, laparoscopic surgery in urology was restricted to the treatment of benign diseases, whereas its role in the management of malignant disease was restricted to purely diagnostic procedures. Only recently has laparoscopy been introduced for the treatment of low stage renal cell carcinoma (RCC), and the data on both surgical efficiency and oncologic efficacy are very promising. Therefore, we present our experience with laparoscopic radical nephrectomy and data from literature. The technique of the transperitoneal approach is described in detail. Retroperitoneoscopy is a good alternative, however. Intact removal of the specimen within an organ bag to avoid tumor spillage is an important detail of our technique. Our experience amounts to radical nephrectomy in 121 patients. The indication was clinical stage T1-T2. Mean operative time and blood loss was 2.4 h and 154 ml, respectively. The rate of minor or major complications was 5% and 4%, respectively. There was no conversion to open surgery in any patient. Mean postoperative hospital stay was 6.1 days. Data on tumor control are available for 73 patients with a mean follow-up of 13.3 months. There was no recurrence within this period. Radical nephrectomy for low-stage RCC is associated with low morbidity and great surgical efficiency. The rates for local recurrences and metastases are low, tumor-specific survival is high. However, there is still a lack of long-term data on large series of patients. Despite this fact, laparoscopy is already widely accepted for this indication, and it is quite likely that it will become the standard treatment.

22
UI - 11877969
AU - Pereverzev AS; Shtsukin DV; Iliukhin IuA
TI - [Long-term results of organ-preserving surgeries for renal cell carcinoma]
SO - Urologiia 2002 Jan-Feb;(1):28-31
The paper presents long-term results of conservative surgical treatment of 148 patients with renal cell carcinoma (RCC). Cancer-specific survival, local recurrence and distant metastases rates were estimated. Overall cancer-specific survival reached 91.8%. For patients with imperative indications this survival was 79.6%, for elective patients--98%. Recurrent RCC was observed in 10(6.8%) patients: imperative group--8(5.4%), elective group--2(1.3%). Distant metastases were detected in 7(4.7%) patients. The elective group had no metastases. General level of multifocality of sporadic renal cancer was 6.7%, for tumors < 4 cm--1.2%. The basic criterion of the decision on organ-saving operation is tumor size under 4 cm. The size of the primary tumor determines the level of local recurrences and distant metastases. To select the optimal group of patients, genetic markers of tumor multifocality should be identified.

23
UI - 12165445
AU - Watanabe N; Kobayashi H; Hirama T; Kikuta A; Koizumi S; Tsuru T; Kaneko
TI - Y Cryptic t(12;15)(p13;q26) producing the ETV6-NTRK3 fusion gene and no loss of IGF2 imprinting in congenital mesoblastic nephroma with trisomy 11: fluorescence in situ hybridization and IGF2 allelic expression analysis.
SO - Cancer Genet Cytogenet 2002 Jul 1;136(1):10-6
AD - Departments of Cancer Chemotherapy and Medicine, Saitama Cancer Center Hospital, Ina, Saitama 362-0806, Japan.
In the present fluorescence in situ hybridization (FISH) study of six congenital mesoblastic nephromas (CMNs) using ETV6 and NTRK3 probes as well as a chromosome 15 painting probe, we identified a cryptic reciprocal translocation, t(12;15)(p13;q26), in one tumor, and an insertion, ins(12;15)(p13;q22q26), in another that were not previously identified by cytogenetic analysis. An interphase FISH study with the same probes detected the ETV6-NTRK3 fusion signal in all three cellular or mixed type tumors, but not in all three classical type tumors. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis detected the ETV6-NTRK3 fusion transcript in the three cellular or mixed type tumors, but not in the three classical type tumors. FISH analysis using a chromosome 11-centromere probe detected trisomy or tetrasomy 11 in all three tumors with the ETV6-NTRK3 fusion signal. To clarify whether IGF2, a paternally expressed gene on chromosome 11, has a certain role in the tumorigenic process of CMN through a loss of imprinting (LOI), we studied IGF2 allelic expression. We found no LOI in two cellular or mixed type tumors or in two classical type tumors, and concluded that the role of the LOI of IGF2 is not essential for the development and progression of CMN with or without trisomy 11. Furthermore, we showed no rearrangements of the MLL gene, which is frequently rearranged in acute leukemia with +11 in the three CMN tumors with +11.

24
UI - 12165447
AU - Nagao K; Yoshihiro S; Matsuyama H; Yamaguchi S; Oba K; Naito K
TI - Clinical significance of allelic loss of chromosome region 5q22.3 approximately q23.2 in nonpapillary renal cell carcinoma.
SO - Cancer Genet Cytogenet 2002 Jul 1;136(1):23-30
AD - Department of Urology, Yamaguchi University School of Medicine, 1-1-1, Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan. katsumai@po.cc.yamaguchi-u.ac.jp
To analyze the clinical significance of copy number gain and loss at chromosome region 5q21 approximately q23, 105 nonpapillary renal cell carcinomas (RCC) were examined by interphase cytogenetic analysis using the dual-color fluorescence in situ hybridization (FISH) technique. DNA probes for D5S23 (5p15.2), cCI5-243 (5q21.2 approximately q21.3), and cCI5-215 (5q22.3 approximately q23.2) were used, and the signals for cCI5-243 and cCI5-215 were compared with those for D5S23 as the numerical control. Aneusomy (three or more copies) of chromosome 5 was found in 22 tumors (21.0%). Aneusomy was significantly correlated with loss at 5q21 approximately q23, while disomy with gain at 5q21 approximately q23 (P<0.05). Aneusomy was also significantly related to poor disease-specific survival (P<0.01). Gain and loss at cCI5-243 were seen in 34 (32.4%) and 59 (56.2%) tumors, respectively, while gain and loss at cCI5-215 occurred in 55 (52.4%) and 45 (42.9%) cases, respectively. The frequency of gain at cCI5-215 was significantly correlated with a smaller tumor diameter (7 cm or less, P<0.05), while loss with a larger one (>7 cm, P<0.05). Both loss at cCI5-215 and aneusomy of chromosome 5 were significantly related to poor disease-specific survival (P<0.05). In conclusion, alterations of chromosome 5 (including allelic loss of 5q22.3 approximately q23.2) could be a useful genetic marker for predicting the patient prognosis of RCC.

25
UI - 11999462
AU - Salvador-Bayarri J; Rodriguez-Villamil L; Imperatore V; Palou Redorta J;
TI - Villavicencio-Mavrich H; Vicente-Rodriguez J Bladder neoplasms after nephroureterectomy: does the surgery of the lower ureter, transurethral resection or open surgery, influence the evolution?
SO - Eur Urol 2002 Jan;41(1):30-3
AD - Departament of Urology, Fundacio Puigvert, Barcelona, Spain. urologia@fundacio-puigvert.es
OBJECTIVE: Nephroureterectomy is the treatment of choice for tumors of the upper urinary tract (UUTT). In 1952, a modified version of this technique was described, involving endoscopic detachment of the ureter followed by nephroureterectomy with a single lumbar incision. We reviewed a retrospective survey to assess whether UUTT patients treated with nephroureterectomy with no prior history of bladder tumor had different rates of incidence or different sites of bladder recurrence according to the specific technique employed. METHODS: Patients were divided into group A, 87 patients who underwent a double incision nephroureterectomy and group B with 58 patients with prior detachment of the ureter. In both groups, incidence was calculated for two variables (bladder tumor recurrences and homolaterality of such recurrences) and chi-square tested. Results: Bladder tumor was diagnosed at follow-up in 39% of patients in group A and 34.5% in group B, with no statistically significant difference (N.S.). Bladder tumor recurrences were homolateral to UUTT in 50% of group A cases and 55% of group B cases (N.S.). CONCLUSIONS: Although this is a retrospective survey of two asynchronous groups, given the similar nature of the UUTT cases in both groups and the fact that no statistically significant differences have been found, it is reasonable to conclude that nephroureterectomy with prior endoscopic detachment of the ureter is a safe and radical procedure.

26
UI - 11912179
AU - Bodmer D; Eleveld M; Kater-Baats E; Janssen I; Janssen B; Weterman M;
TI - Schoenmakers E; Nickerson M; Linehan M; Zbar B; van Kessel AG Disruption of a novel MFS transporter gene, DIRC2, by a familial renal cell carcinoma-associated t(2;3)(q35;q21).
SO - Hum Mol Genet 2002 Mar 15;11(6):641-9
AD - Department of Human Genetics, University Medical Center Nijmegen, Nijmegen, The Netherlands. d.bodmer@antrg.azn.nl
Previously, we described a family with a significantly increased predisposition for renal cell cancer co-segregating with a t(2;3)(q35;q21) chromosomal translocation. Several primary tumors of the clear cell type from different family members were analyzed at a molecular level. Loss of the derivative chromosome 3 was consistently found. In addition, different somatic Von Hippel Lindau (VHL) gene mutations were observed in most of the tumors analyzed, even within the same patient. Based on these results a multistep tumorigenesis model was proposed in which (non-disjunctional) loss of the derivative chromosome 3 represents an early event and somatic mutation of the VHL gene represents a late event related to tumor progression. More recently, however, we noted that these two anomalies were absent in at least one early-stage tumor sample that we tested. Similar results were obtained in another family with renal cell cancer and t(3;6)(q12;q15), thus suggesting that another genetic event may precede these two oncogenetic steps. We speculate that deregulation of a gene(s) located at or near the translocation breakpoint may act as such. In order to identify such genes, a detailed physical map encompassing the 3q21 breakpoint region was constructed. Through a subsequent positional cloning effort we found that this breakpoint targets a hitherto unidentified gene, designated DIRC2 (disrupted in renal cancer 2). Computer predictions of the putative DIRC2 protein showed significant homology to different members of the major facilitator superfamily (MFS) of transporters. Based on additional DIRC2 expression and mutation analyses, we propose that the observed gene disruption may result in haplo-insufficiency and, through this mechanism, in the onset of tumor growth.

27
UI - 12101482

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