• Increased myeloperoxidase and lipid peroxide-modified protein in gynecological malignancies.

• Methylation of adenomatous polyposis coli in endometrial cancer occurs more frequently in tumors with microsatellite instability phenotype.

• The significance of the amount of myometrial invasion in patients with Stage IB endometrial carcinoma.

• Dual breast cancers followed by endometrial cancer.

• Stage II endometrial carcinoma: prognostic factors and risk classification in 170 patients.

• What do we expect from imaging?

• Imaging of cancer of the endometrium.

• Postsurgical pelvis: treatment follow-up.

• Tumor invasion and metastasis--nature or nurture?

• Hormonal treatment of endometrial carcinoma.

• Genes involved in DNA repair are mutational targets in endometrial cancers with microsatellite instability.

• Common polymorphisms and somatic mutations in human base excision repair genes in ovarian and endometrial cancers.

• A review of selective estrogen receptor modulators in the treatment of breast and endometrial cancer.

• Estrogen receptor expression in an endometrial stromal sarcoma after tamoxifen therapy.

• Prognostic value of p53, c-erb-B2 and MIB-1 in endometrial carcinoma.

• Recurrent low grade endometrial stromal sarcoma in ascitic fluid.

• Cytologic diagnosis of low grade endometrial stromal sarcoma by staining for estrogen and progesterone receptors.

• Endometrial carcinoma after endometrial ablation: high-risk factors predicting its occurrence.

• Intrauterine scarring as a result of total endometrial ablation could delay the diagnosis of endometrial cancer.

• hMLH1 promoter hypermethylation in microsatellite instability-positive endometrial carcinoma. Cause or consequence?

• hMLH1 promoter hypermethylation is an early event in human endometrial tumorigenesis.

• Accuracy of outpatient endometrial biopsy in the diagnosis of endometrial cancer: a systematic quantitative review.

• Pitfalls of radiation survey after brachytherapy implant removal preceding Tl-201 study.

• Minilaparotomy in early stage endometrial cancer: an alternative to standard and laparoscopic treatment.

• Endometrial adenocarcinoma arising from endometriosis of the rectosigmoid colon.

• Endometrial carcinoma diagnosed by positron emission tomography: a case report.

• [Diagnostic image (87). A tattooed woman with salpingitis]

• The effects of tamoxifen on proliferation and steroid receptor expression in postmenopausal endometrium.

• Endometrial cancer incidence in relation to electric blanket use.

• The waiting time paradox: population based retrospective study of treatment delay and survival of women with endometrial cancer in

• Hormone receptor immunohistochemistry and human papillomavirus in situ hybridization are useful for distinguishing endocervical and endometrial

1
UI - 11813987
AU - Song M; Santanam N
TI - Increased myeloperoxidase and lipid peroxide-modified protein in gynecological malignancies.
SO - Antioxid Redox Signal 2001 Dec;3(6):1139-46
AD - Department of Gynecology and Obstetrics, Emory University, School of Medicine, Atlanta, GA 30322, USA.
Oxidative stress has been implicated in several diseases, including cancer. Oxidants induce oncogenes and their products associated with cell growth. Even though epidemiological studies implicate oxidants in promoting cancer, there is still a lack of in vivo evidence for the same. In this study, we measured the levels of myeloperoxidase (MPO), an enzyme associated with oxidation and autoantibodies to lipid peroxide-modified protein (LOOH-RSA), in the plasma of subjects with gynecological cancers. The gynecological cancer subjects (n = 201) had higher plasma MPO and LOOH-RSA levels compared with control subjects (n = 60). Immunohistochemical analysis of tissues revealed that immunostaining for MPO and LOOH-RSA was higher in cancer tissues compared with controls. The staining was specific to cell types and not ubiquitously present. Neutrophils, monocytes/macrophages, and natural killer cells have been proposed to play a role in cancer promotion and progression. This study proposes a role for oxidative stress and especially MPO in cancer.

2
UI - 12097272
AU - Zysman M; Saka A; Millar A; Knight J; Chapman W; Bapat B
TI - Methylation of adenomatous polyposis coli in endometrial cancer occurs more frequently in tumors with microsatellite instability phenotype.
SO - Cancer Res 2002 Jul 1;62(13):3663-6
AD - Samuel Lunenfeld Research Institute, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada.
Differential methylation is an important epigenetic control mechanism, which has been implicated in the development of a variety of cancers. Methylation of promoter regions of normally unmethylated tumor suppressor genes leads to transcriptional inactivation and ultimately to tumor formation. We hypothesized that epigenetic inactivation of adenomatous polyposis coli (APC), a key player in the suppressor pathway, may contribute to the development of endometrial cancer. We investigated APC methylation in endometrial adenocarcinoma specimens obtained from a series of patients (n = 114) and compared methylation profiles with microsatellite instability (MSI+) status. DNA microdissected from formalin-fixed, paraffin-embedded matched normal and tumor specimens, and a subset of associated endometrial hyperplasia was subjected to methylation-specific PCR of the APC promoter 1A region. Tumor-specific hypermethylation of APC with corresponding unmethylated normal endometrial tissue occurred in 43% (17 of 40) of MSI+ cases (P = 0.0007) and 16% (12 of 74) of microsatellite stable cases (P = 0.04). Interestingly, tumor tissue was unmethylated with normal tissue displaying APC methylation in 4% (5 of 114, 2MSI+ and 3 microsatellite stable) of cases. Endometrial cell lines AN3CA, RL95-2, and HEC-1B all displayed exclusive methylation of promoter 1A, and treatment of the AN3CA cell line with the demethylating agent 5-aza-2'-deoxycytidine exhibited re-expression of APC as confirmed by RT-PCR analysis. Our results demonstrate APC methylation in endometrial cancer for the first time and show that APC hypermethylation occurs at an increased frequency in MSI+ endometrial tumors (P = 0.01).

3
UI - 12124832
AU - Alektiar KM; McKee A; Lin O; Venkatraman E; Zelefsky MJ; Mychalczak BR;
TI - McKee B; Hoskins WJ; Barakat RR The significance of the amount of myometrial invasion in patients with Stage IB endometrial carcinoma.
SO - Cancer 2002 Jul 15;95(2):316-21
AD - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA. alektiak@mskcc.org
BACKGROUND: The 1988 International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial carcinoma defined Stage IB as disease with invasion of less than one-half of the myometrium, although most of the data on prognostic factors are based on invasion of the inner one-third, middle one-third, or outer one-third of the myometrium. The objective of this study was to determine whether the depth of myometrial invasion is correlated with outcome in patients with Stage IB endometrial carcinoma. METHODS: Between November, 1987 and June, 1998, 251 patients with Stage IB endometrioid adenocarcinoma of the uterus underwent simple hysterectomy followed by intravaginal brachytherapy. The depth of myometrial invasion was less than or equal to one-third (Group I) in 191 of 251 patients (79%) and greater than one-third to less than one-half (Group II) in 52 of 251 patients (21%). Comprehensive surgical staging (CSS) was done in 12% of patients. The two groups were balanced with regard to age (< 60 years vs. > or = 60 years), FIGO grade, lower uterine segment involvement (LUSI), CSS, and the use of postoperative external-beam radiation. The rate of capillary-like space invasion (CLSI), however, was 9% in Group I compared with 25% in Group II (P = 0.002). The median follow-up was 58 months. RESULTS: The overall 5-year actuarial local-regional control (LRC), disease free (DFS) survival, and overall survival (OS) rates were 95%, 92%, and 92%, respectively. These end points, however, did not vary significantly between the two groups. The 5-year LRC, DFS, and OS rates in Groups I and II were 96% versus 95%, respectively (P = 0.9); 92% versus 94%, respectively (P = 0.7); and 92% versus 90%, respectively (P = 0.5). On multivariate analysis, the influence on outcome of age, grade, amount of myometrial invasion, LUSI, and CLSI was evaluated. Only age > or = 60 years and FIGO Grade 3 were correlated with poor DFS (P = 0.02 and P = 0.03, respectively) and OS (P = 0.001 and P = 0.01, respectively). CONCLUSIONS: Based on this study, in patients with Stage IB endometrial carcinoma, the amount of myometrial invasion, defined as invasion less than or equal to one-third of the myometrium versus invasion greater than one-third and less than one-half of the myometrium, did not appear to influence outcome. Age > or = 60 years and FIGO Grade 3, however, emerged as independent prognostic factors for poor DFS and OS. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10660

4
UI - 12082808
AU - Dimitrievich E; Sterzinger A
TI - Dual breast cancers followed by endometrial cancer.
SO - S D J Med 2002 Jun;55(6):227-9
AD - USD School of Medicine, Sioux Falls, USA.
Two cases in which dual breast cancers occurred at several years interval, followed by endometrial cancer are described. The risk factors for dual breast cancers, the association between breast and endometrial cancer, and the association of tamoxifen therapy with endometrial cancer, and future cancer risk will be briefly discussed.

5
UI - 12095551
AU - Pitson G; Colgan T; Levin W; Lockwood G; Manchul L; Milosevic M; Murphy
TI - J; Fyles A Stage II endometrial carcinoma: prognostic factors and risk classification in 170 patients.
SO - Int J Radiat Oncol Biol Phys 2002 Jul 15;53(4):862-7
AD - Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada.
PURPOSE: Factors affecting outcome in patients with surgicopathologic Stage II endometrial cancer are poorly defined. The purpose of this study was to determine prognostic factors in a series of patients treated according to standardized protocols at a single institution. METHODS AND MATERIALS: One hundred and seventy patients referred to Princess Margaret Hospital after hysterectomy between 1984 and 1995 were retrospectively reviewed. One hundred and twenty patients received postoperative external beam radiotherapy and brachytherapy, 18 received external beam radiotherapy alone, five received brachytherapy alone, and 27 had no radiotherapy. RESULTS: With a median follow-up of 5.1 years, overall and disease-free survival (DFS) at 5 years was 77% and 68%, respectively, and 24% of patients had relapsed. Significant independent adverse factors for DFS included age >65 (p = 0.0001), FIGO Stage IIB (p = 0.02), and capillary-lymphatic space (CLS) involvement (p = 0.0007). Prognostic factors for relapse were age (p = 0.0008), histologic grade (p = 0.01), and CLS (p = 0.01). A prognostic model based on the number of adverse prognostic factors (0-3) revealed that the 5-year survival rates for the four groups were as follows: 0%-85%, 1%-77%, 2%-55%, and 3%-11%. Combining the groups with 0 or 1 adverse factors resulted in a three-group variable that was strongly related to DFS (p < 0.0001). CONCLUSIONS: Patient age, stage, and CLS were significant factors for DFS, and age, grade, and CLS predicted time to relapse in Stage II endometrial cancer. A prognostic model for DFS using these factors can provide clinically meaningful outcome predictions.

6
UI - 12117191
AU - Barakat RR; Hricak H
TI - What do we expect from imaging?
SO - Radiol Clin North Am 2002 May;40(3):521-6, vii
AD - Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. barakatr@mskcc.org
The objectives of imaging in gynecologic cancer include tumor detection, tumor diagnosis, staging, and follow-up. In addition, both monitoring response to treatment and differentiating tumor recurrence from post-treatment changes are important indications for imaging. In 2001 it was estimated that there would be 38,300 cases of endometrial cancer, 23,400 cases of ovarian cancer, and 12,900 cases of cervical cancer. This article reviews what information is required by the practicing gynecologist or gynecologic oncologist prior to surgery and briefly summarizes state-of-the-art imaging in answering clinically pertinent questions.

7
UI - 12117193
AU - Ascher SM; Reinhold C
TI - Imaging of cancer of the endometrium.
SO - Radiol Clin North Am 2002 May;40(3):563-76
AD - Department of Radiology, Georgetown University Hospital, Washington, DC 20007-2197, USA. aschers@gunet.georgetown.edu
Transvaginal US is often the initial imaging examination for women with dysfunctional (postmenopausal or intermenstrual) uterine bleeding. However, once the diagnosis of endometrial cancer has been made, contrast-enhanced MRI should be performed in patients who require multifactorial assessment (eg, depth of myometrial invasion, cervical involvement, lymph node metastasis). The results of contrast-enhanced MRI help distinguish patients who need more aggressive therapy and referral to a gynecologic oncologist from those who will do well treated by a community gynecologist.

8
UI - 12117198
AU - Sugimura K; Okizuka H
TI - Postsurgical pelvis: treatment follow-up.
SO - Radiol Clin North Am 2002 May;40(3):659-80, viii
AD - Department of Radiology, Kobe University Graduate School of Medicine, Japan. sugimura@kobe-u.ac.jp
Imaging for recurrence and complications of gynecologic malignancies following treatment with radical hysterectomy, chemotherapy, and radiation therapy has become an important determinant for treatment options available to patients. MR imaging and computed tomography can be used to provide evidence of limited local disease recurrence and thereby identify disease that is still potentially curable with adjuvant treatments. This article examines the imaging modalities currently used to detect recurrence and assist in making treatment changes for gynecologic malignancies and presents specific patient findings following definitive primary treatment of uterine cancer and ovarian cancer with radical hysterectomy, radiation therapy, or chemotherapy.

9
UI - 11774182
AU - Rosser RJ
TI - Tumor invasion and metastasis--nature or nurture?
SO - Hum Pathol 2001 Dec;32(12):1416-7

10
UI - 12113059
AU - Baekelandt M
TI - Hormonal treatment of endometrial carcinoma.
SO - Expert Rev Anticancer Ther 2002 Feb;2(1):106-12
AD - Dept. Gynecologic Oncology, Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway. mark.baekelandt@klinmed.uio.no
Endometrial cancer has typically been regarded as a relatively benign disease. However, survival rates for patients with advanced-stage or recurrent disease are very poor and more adequate systemic treatment is certainly needed. Being a tumor that arises from a hormone responsive tissue, endometrial cancer is a logical target for endocrine manipulation. This article gives an overview of our current knowledge on hormonal therapy and highlights the large potential for improvement in results of such therapy. Target areas for future research are described.

11
UI - 12124347
AU - Vassileva V; Millar A; Briollais L; Chapman W; Bapat B
TI - Genes involved in DNA repair are mutational targets in endometrial cancers with microsatellite instability.
SO - Cancer Res 2002 Jul 15;62(14):4095-9
AD - Samuel Lunenfeld Research Institute, Toronto, Ontario, M5G 1X5 Canada.
Microsatellite instability (MSI) is observed in a subset of endometrial cancers (ECs) and is attributed to defects in mismatch repair. Mismatch repair deficiency allows for accumulation of mutations in the coding repeats of key target genes, which may be involved in the initiation and progression of MSI+ EC. We examined genes implicated in DNA repair pathways in 38 MSI-high (MSI-H), 10 MSI-low, 25 microsatellite stable ECs, and a selected panel of associated premalignant hyperplasias. Genetic alterations were correlated to histopathological data, including tumor grade and stage. Somatic frameshift mutations were observed in hMLH3, hMSH3, hMSH6, CHK1, and BAX genes in MSI-H endometrial hyperplasias and cancers, whereas mutations in ATR and CDC25C were observed only in MSI-H ECs. Increased mutation frequency in DNA damage response pathway genes including ATR, CHK1, and BAX demonstrated a significant trend with advancing tumor grade (P < 0.05). Our observations of the same mutations at short coding mononucleotide repeats in both premalignant lesions and tumors and association of increased frequency of mutation accumulation with advancing tumor grade suggest that these alterations may play a role in the development and progression of MSI+ EC.

12
UI - 11465542
AU - Pieretti M; Khattar NH; Smith SA
TI - Common polymorphisms and somatic mutations in human base excision repair genes in ovarian and endometrial cancers.
SO - Mutat Res 2001 Jan;432(3-4):53-9
AD - Department of Pathology, University of Kentucky, Lexington 40536, USA. mpieretti@usamail.usouthal.edu
The purpose of this study was to determine whether the human APEX and OGG1 genes, encoding proteins important in base excision repair (BER) of DNA, contain nucleotide sequence polymorphisms or are mutated somatically in tumors from women diagnosed with ovarian or endometrial cancer. Based upon the analysis of germline DNA from 83 individuals, 63 with ovarian cancer and 20 with endometrial cancer, we found two missense polymorphisms in APEX (Q51H and D 148E) and two missense (A3P and S326C) and one intronic (Exon 5-15 bp) polymorphism in OGG1. The frequencies of the various alleles (in the ovarian and endometrial cancer patients combined) were 4.8% for 51-His and 56.2% for 148-Glu in APEX, and 1.0% for 3-Pro and 20.0% for 326-Cys in OGG1. Somatic mutations in APEX (P112L, W188X and R237C) were identified in three of 20 endometrial tumors, but no mutations were identified in APEX in 43 ovarian tumors, or in OGG1 at either tumor site. Given the crucial role of the APEX and OGG1 proteins in BER of oxidative DNA damage, the identified polymorphisms are good candidates for genetic epidemiologic studies of cancer susceptibility, while the finding that three of 20 (15%) endometrial tumors have somatic mutations in APEX suggests that inactivation of the BER pathway is important for the development of endometrial cancer in at least a subset of cases.

13
UI - 12138407
AU - Chan S
TI - A review of selective estrogen receptor modulators in the treatment of breast and endometrial cancer.
SO - Semin Oncol 2002 Jun;29(3 Suppl 11):129-33
AD - Nottingham City Hospital, Nottingham, United Kingdom.
The understanding of how estrogen affects different body tissues by selective actions on the two subtypes of estrogen receptors (alpha and beta) has created the possibility of targeted therapy by the manufacturing of a group of compounds known as selective estrogen receptor modulators. The goal of an ideal selective estrogen receptor modulator that has all the beneficial effects of estrogen receptor modulation without adverse side effects seems increasingly achievable with improving drug design. The clinical findings for the new selective estrogen receptor modulator, arzoxifene, which has been shown to be highly active in the treatment of advanced breast cancer as well as advanced endometrial cancer, has confirmed the value of selective targeting of the estrogen receptors, and may herald a new era in endocrine therapy in clinical oncology. Copyright 2002, Elsevier Science (USA). All rights reserved.

14
UI - 11874071
AU - Liao JB; Lin JY
TI - Estrogen receptor expression in an endometrial stromal sarcoma after tamoxifen therapy.
SO - Eur J Gynaecol Oncol 2001;22(6):417-9
AD - Department of Obstetrics and Gynecology, The George Washington University Medical Center, Washington, DC, USA.
INTRODUCTION: Several cases of low-grade endometrial stromal sarcomas in women with breast cancer have been reported to be associated with tamoxifen therapy. Estrogen receptor expression has been used to characterize the partial estrogenic action of tamoxifen on the endometrium and has been found in tamoxifen-associated endometrial pathologies. CASE: A low-grade endometrial stromal sarcoma in a woman with a history of breast cancer treated with adjuvant tamoxifen is presented. Steroid receptor studies performed on the tumor were negative for estrogen and positive for progesterone. CONCLUSION: The absence of estrogen receptor expression suggests that endometrial stromal sarcomas are not necessarily caused by the estrogenic properties of tamoxifen.

15
UI - 11874080
AU - Cherchi PL; Marras V; Capobianco G; Ambrosini G; Piga MD; Fadda GM;
TI - Rosas N; Dessole S Prognostic value of p53, c-erb-B2 and MIB-1 in endometrial carcinoma.
SO - Eur J Gynaecol Oncol 2001;22(6):451-3
AD - Department of Pharmacology, Gynaecology and Obstetrics, University of Sassari, Italy.
OBJECTIVE: To assess the immunohistochemical expression of p53 protein, a tumour suppressor gene of the oncogene c-erb-B2 and MIB-1 proliferation marker (Ki-67 antigen) in endometrial carcinoma. METHODS: We studied 29 cases of endometrial carcinoma in which the p53, c-erb-B2 and MIB-1/Ki-67 antigens were investigated by an immunohistochemical method. We evaluated the correlations among the immunohistochemical positivity and the grading, depth of myometrial invasion, stage of the neoplasia and follow-up. RESULTS: Both p53 and c-erb-B2 were positive in 16 out of 29 cases (55.2%), whereas MIB-1 was positive in 19 out of 29 cases (65.5%). All these three antigens showed a positive correlation with the grading, myometrial invasion and FIGO stage. Regarding follow-up, p53, c-erb-B2 and MIB-1 were, respectively, positive in 100%, 83.4% and 66.7% of neoplasias of patients who died of disease whereas they were positive in 40%, 40% and 60%, respectively, of tumours of patients with no evidence of disease. CONCLUSION: The overexpression of p53, c-erb-B2 and MIB-1 seem to indicate a more malignant tumour phenotype.

16
UI - 12146054
AU - Yokosuka K; Abe S
TI - Recurrent low grade endometrial stromal sarcoma in ascitic fluid.
SO - Acta Cytol 2002 Jul-Aug;46(4):785-7

17
UI - 12146057
AU - Reich O; Pickel H; Regauer S
TI - Cytologic diagnosis of low grade endometrial stromal sarcoma by staining for estrogen and progesterone receptors.
SO - Acta Cytol 2002 Jul-Aug;46(4):790-2

18
UI - 9757952
AU - Valle RF; Baggish MS
TI - Endometrial carcinoma after endometrial ablation: high-risk factors predicting its occurrence.
SO - Am J Obstet Gynecol 1998 Sep;179(3 Pt 1):569-72
AD - Department of Obstetrics and Gynecology, Northwestern University Medical School, Chicago, Illinois, USA.
Our purpose was to review reported cases of endometrial carcinoma after endometrial ablation and to evaluate high-risk factors predicting its occurrence. We present guidelines for the treatment of abnormal uterine bleeding unresponsive to medical therapy in this high-risk group of patients. Eight detailed reports on endometrial carcinoma after endometrial ablation were reviewed. The indications, methods of treatment, follow-up, and associated high-risk factors for endometrial carcinoma were analyzed. A focused list of high-risk factors for endometrial carcinoma was developed on the basis of the data collected. Guidelines were established to enable surgeons to minimize the risks of subsequent uterine cancer in women with abnormal uterine bleeding that is unresponsive to medical therapy (ie, candidates for ablation). Women who had endometrial carcinoma develop after ablation had predictive high-risk factors for subsequent neoplasia, and all eventually underwent a hysterectomy. Women with abnormal uterine bleeding and high-risk factors for endometrial carcinoma who did not respond to medical treatment may safely undergo endometrial ablation but must have a preablation biopsy indicating normal endometrium. Persistent hyperplasia unresponsive to hormonal therapy should influence the selection of a hysterectomy. Careful screening of patients before undergoing endometrial destructive procedures is prescient because minimally invasive, nonhysteroscopic ablative techniques are now emerging.

19
UI - 10368513
AU - McCausland AM; McCausland VM
TI - Intrauterine scarring as a result of total endometrial ablation could delay the diagnosis of endometrial cancer.
SO - Am J Obstet Gynecol 1999 Jun;180(6 Pt 1):1598-9

20
UI - 10550292
AU - Ellenson LH
TI - hMLH1 promoter hypermethylation in microsatellite instability-positive endometrial carcinoma. Cause or consequence?
SO - Am J Pathol 1999 Nov;155(5):1399-402
AD - Department of Pathology, Weill Medical College of Cornell University, New York, New York, USA. lhellens@mail.med.cornell.edu

21
UI - 10550333
AU - Esteller M; Catasus L; Matias-Guiu X; Mutter GL; Prat J; Baylin SB;
TI - Herman JG hMLH1 promoter hypermethylation is an early event in human endometrial tumorigenesis.
SO - Am J Pathol 1999 Nov;155(5):1767-72
AD - Department of Tumor Biology, The Johns Hopkins Oncology Center, Baltimore, Maryland, USA.
It has recently been suggested that silencing of the hMLH1 gene by promoter hypermethylation is the mechanism underlying the presence of the microsatellite instability (MSI) phenotype in sporadic colon and endometrial carcinomas. To determine whether hMLH1 promoter hypermethylation is a relatively early event in endometrial tumorigenesis we evaluated endometrial hyperplasia (EH) characterized as simple, complex, and atypical (the direct precursor of endometrial carcinoma) for hMLH1 aberrant methylation. In addition, we studied the hMLH1, hMSH2, hMSH3, and hMSH6 promoter methylation and MSI status of those endometrial carcinomas with synchronous hyperplasias and those without them. We found that 11 of 12 (91%) cases of endometrial carcinoma (EC) displaying MSI had hMLH1 promoter hypermethylation, whereas aberrant methylation of any of the other mismatch repair genes was not observed. All 15 cases of EC without MSI were unmethylated at hMLH1. Abnormal methylation of hMLH1 was also present in 8 of 116 (7%) cases of EH and was restricted primarily to the atypical endometrial hyperplasia (AEH) type with coexisting endometrial carcinoma. In this set, half of EH methylated at hMLH1 displayed MSI, whereas none of the unmethylated EH had MSI. Our data suggest that hypermethylation of hMLH1 can be an early event in the pathogenesis of EC, preceding the development of an apparent MSI phenotype in a subset of cases.

22
UI - 11950187
AU - Clark TJ; Mann CH; Shah N; Khan KS; Song F; Gupta JK
TI - Accuracy of outpatient endometrial biopsy in the diagnosis of endometrial cancer: a systematic quantitative review.
SO - BJOG 2002 Mar;109(3):313-21
AD - Academic Department of Obstetrics and Gynaecology, Birmingham Women's Hospital, UK.
OBJECTIVE: To determine the accuracy of outpatient endometrial biopsy in diagnosing endometrial cancer in women with abnormal uterine bleeding. DESIGN: A systematic quantitative review of published research. METHODS: Studies were selected if accuracy of outpatient endometrial biopsy was estimated compared with a reference standard. Diagnostic accuracy was determined by pooled likelihood ratios for positive and negative test results. There were 1013 subjects in 13 diagnostic evaluations reported in 11 primary studies. RESULTS: A positive test result on outpatient biopsy diagnosed endometrial cancer with a pooled likelihood ratio of 66.48 (95% CI 30.04-147.13) while a negative test result had a pooled likelihood ratio of 0.14 (95% CI 0.08-0.27). The post test probability of endometrial cancer was 81.7% (95% CI 59.7%-92.9%) for a positive test and 0.9% (95% CI 0.4%-2.4%) for a negative test. CONCLUSION: Outpatient endometrial biopsy has a high overall accuracy in diagnosing endometrial cancer when an adequate specimen is obtained. A positive test result is more accurate for ruling in disease than a negative test result is for ruling it out. Therefore, in cases of abnormal uterine bleeding where symptoms persist despite negative biopsy, further evaluation will be warranted.

23
UI - 12072776
AU - Gaston RC; Arnold CD; Ahluwalia BD; Sonnad JR; Macdurmon GW; Gold MA;
TI - Parry CK; Montebello JF; Mayr NA Pitfalls of radiation survey after brachytherapy implant removal preceding Tl-201 study.
SO - Clin Nucl Med 2002 Jul;27(7):494-8
AD - Radiation Oncology Center, Department of Radiological Sciences, Oklahoma University Health Sciences Center, Oklahoma City 73104, USA.
An unexpected elevated postimplant radiation survey is described in an elderly patient with an interstitial low-dose-rate iridium-192 (Ir-192) needle implant for endometrial cancer. The elevated activity was related to prolonged clearance of Tl-201 from a cardiac study that had been performed 7 days earlier. The Tl-201 accumulated in the soft tissue, particularly the colon, resulting in increased survey readings over the abdomen and raising concern that an Ir-192 source remained within the patient. This case shows that delayed excretion of a diagnostic radionuclide agent can cause elevated activity high enough to confound postradiotherapy implant survey readings. The estimated surface exposure from a single iridium source left in the pelvis was determined using a phantom study. Possible factors causing decreased excretion of Tl-201 in a patient with heart disease, arteriosclerotic vascular disease, previous pelvic radiation therapy, and a brachytherapy procedure are discussed. A preloading radiation survey is recommended in patients who have had previous nuclear medicine studies involving radionuclides with long half-lives.

24
UI - 12144825
AU - Fagotti A; Ferrandina G; Longo R; Mancuso S; Scambia G
TI - Minilaparotomy in early stage endometrial cancer: an alternative to standard and laparoscopic treatment.
SO - Gynecol Oncol 2002 Aug;86(2):177-83
AD - Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
OBJECTIVE: Our objective was to determine whether minilaparotomy could be a safe and feasible approach for the surgical treatment of early endometrial cancer patients and whether it could be considered a valid alternative to the laparoscopic treatment. METHODS: A pilot study of 50 consecutive patients with FIGO stage I-IV endometrial cancer undergoing All patients were evaluated for a minimal transabdominal approach. Exclusion criteria were considered: special histotype, poorly differentiated tumors, clinical stage >/=Ic, Ca125 >35 U/ml, BMI >30, lymph nodal involvement assessed by MRI, and severe cardiopulmonary disease precluding steep Trendelenburg position. RESULTS: Twenty-six (52%) cases were considered eligible for minilaparotomy. The mean age was 55.4 years and the mean BMI was 24.1. All patients underwent TAH, BSO, pelvic lymphadenectomy +/- omental or peritoneal biopsy. A mean number of 28 pelvic lymph nodes were removed. The mean operative time was 113.0 min and the mean intraoperative blood loss was 220.0 ml. There was 1 severe operative hemorrhage and 1 patient needed postoperative blood transfusion. No immediate complications of wound infection or separation occurred. The mean hospital stay was 3.4 days. Intra- and postoperative parameters were compared to laparotomy controls and literature data on laparoscopy, showing substantially comparable results. CONCLUSION: Minilaparotomy is a feasible alternative to the standard treatment in endometrial cancer patients. It offers the patient a cost-effective procedure that avoids many of the potential complications of standard therapy, prevents long hospital recovery periods, and accomplishes all of the important goals of standard recommendations.

25
UI - 12144831
AU - Jones KD; Owen E; Berresford A; Sutton C
TI - Endometrial adenocarcinoma arising from endometriosis of the rectosigmoid colon.
SO - Gynecol Oncol 2002 Aug;86(2):220-2
AD - The Royal Surrey County Hospital, Surrey, United Kingdom. kjones@rschguildford.freeserve.co.uk
BACKGROUND: Only 21.3% of cases of malignant transformation of endometriosis occur at extragonadal pelvic sites. Forty cases of endometriosis-associated intestinal tumors are reported in the literature. Of these, 17 cases are primary adenocarcinomas arising in the rectosigmoid colon. In 8 of the 17 case reports the patients were using unopposed estrogen replacement therapy. CASE: The patient had previously undergone a total abdominal hysterectomy and bilateral salpingo-oophorectomy for deeply infiltrating rectovaginal endometriosis, and was using estrogen replacement therapy. She presented with rectal bleeding 12 years later, and a polyp was detected arising from the sigmoid colon. A biopsy detected malignant transformation of endometriosis to adenocarcinoma. CONCLUSION: This is the ninth case of a patient with this condition reported in the literature.

26
UI - 12144832
AU - Lentz SS
TI - Endometrial carcinoma diagnosed by positron emission tomography: a case report.
SO - Gynecol Oncol 2002 Aug;86(2):223-4
AD - Department of Obstetrics and Gynecology, Wake Forest University School of Medicien, Winston-Salem, North Carolina 27157, USA. slentz@wfubmc.edu
BACKGROUND: Positron emission tomography (PET) scanning utilizes the recognized tumor metabolic property of increased glycolysis with the radioactive decay of 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) and generation of gamma radiation to provide quantitative tumor imaging. PET scanning has proven useful in the evaluation and staging of malignancies including malignant melanoma. CASE REPORT: As part of the preoperative staging evaluation a PET scan was performed in a 76-year-old white female with a biopsy-proven malignant melanoma on the posterior thorax. Physiologic uptake was delineated, and in addition, an area of increased uptake of FDG in the pelvis anatomically consistent with the uterus was observed. Subsequent endometrial sampling revealed a moderately differentiated endometrioid adenocarcinoma. Surgical staging revealed a stage IB, grade 2 lesion. CONCLUSION: This is the first case report of an endometrial carcinoma diagnosed incidentally by positron emission tomography in an asymptomatic patient.

27
UI - 12038223
AU - Lammes FB
TI - [Diagnostic image (87). A tattooed woman with salpingitis]
SO - Ned Tijdschr Geneeskd 2002 May 4;146(18):849
AD - Gynaecoloog, Peppinghof 3, 1391 BA Abcoude.
In a 61-year-old woman uterus and adnexa were surgically removed because of endometrial carcinoma. In the tuba accumulation of pigment-laden macrophages was observed. She had been a victim of World War II concentration camp gynaecological experiments. Her left forearm showed the Auschwitz Jew tattoo.

28
UI - 12101196
AU - Mourits MJ; Ten Hoor KA; van der Zee AG; Willemse PH; de Vries EG;
TI - Hollema H The effects of tamoxifen on proliferation and steroid receptor expression in postmenopausal endometrium.
SO - J Clin Pathol 2002 Jul;55(7):514-9
AD - Department of Gynaecology, University Hospital Groningen, Hanzeplein 1, The Netherlands. m.j.e.mourits@og.azg.nl
AIM: To study the effects of tamoxifen on the proliferation index and oestrogen receptor (ER) and progesterone receptor (PR) expression in postmenopausal endometrium. METHODS: A total of 125 endometrial specimens of postmenopausal women, comprising benign endometria from tamoxifen users (n = 35) and non-users (n = 24), and endometrial cancer from tamoxifen users (n = 15) and non-users (n = 51), were immunohistochemically examined using MIB-1, anti-ER, and anti-PR antibodies in endometrial epithelium and stroma. RESULTS: In benign endometrium the mean MIB-1 index in the epithelium was higher in tamoxifen users than in non-users (mean, 13% (SD, 13%) v mean, 2% (SD, 2%); p < 0.05), whereas in endometrial cancer the MIB-1 index was higher, but similar in tamoxifen users and non-users (mean, 32% (SD, 24%) and mean, 35% (SD, 18%)). The expression of ER was comparably high in benign epithelium from tamoxifen users and non-users (97% and 92%, respectively), but in endometrial cancer it was lower in tamoxifen users (60% and 88%; p < 0.05). The expression of PR in stromal cells was higher in tamoxifen users, both in benign (84% v 54%) and in malignant endometrium (33% v 10%; p < 0.05). CONCLUSION: The proliferation index (as measured by MIB-1) in benign endometrial epithelium is higher in tamoxifen users than in non-users, and this might play a role in the reported higher incidence of endometrial cancer in postmenopausal tamoxifen users. The increased expression of PR in stroma from tamoxifen users with both benign and malignant endometrium demonstrates an additional oestrogenic effect of tamoxifen on the endometrial stroma.

29
UI - 12142261
AU - McElroy JA; Newcomb PA; Trentham-Dietz A; Hampton JM; Kanarek MS;
TI - Remington PL Endometrial cancer incidence in relation to electric blanket use.
SO - Am J Epidemiol 2002 Aug 1;156(3):262-7
AD - University of Wisconsin Comprehensive Cancer Center, Madison, WI 53726, USA. jamcelroy@wisc.edu
Endometrial cancer is associated with endogenous and exogenous estrogen excess. Some investigators have posited that electromagnetic fields may influence cancer risk through estrogenic hormonal mechanisms; however, there have been no studies reporting on electric blanket exposure in relation to endometrial cancer. The authors examined this possible association between endometrial cancer risk and electric blanket or mattress cover use as part of a population-based, case-control study. This analysis included incident endometrial cancer cases 40-79 years of age, interviewed during 1994 (n = 148; response rate, 87%) and identified from the Wisconsin tumor registry. Female controls of similar age were randomly selected from population lists (n = 659; response rate, 85%). Information regarding electric blanket and mattress cover use and endometrial cancer risk factors was obtained through structured telephone interviews approximately 1 year after diagnosis. After adjustment for age, body mass index, and postmenopausal hormone use, the risk of endometrial cancer was similar among ever users (odds ratio = 1.04, 95% confidence interval: 0.70, 1.55) and among current users (odds ratio = 0.87, 95% confidence interval: 0.49, 1.54) as compared with never users. Despite its small size and potential misclassification of exposure, this study provides evidence against an association between electric blanket or mattress cover use and endometrial cancer.

30
UI - 12142308
AU - Crawford SC; Davis JA; Siddiqui NA; de Caestecker L; Gillis CR; Hole D;
TI - Penney G The waiting time paradox: population based retrospective study of treatment delay and survival of women with endometrial cancer in Scotland.
SO - BMJ 2002 Jul 27;325(7357):196
AD - Department of Gynaecological Oncology, Stobhill Hospital, Glasgow G21 3UW. S.C.Crawford@btinternet.com

31
UI - 12170086
AU - Staebler A; Sherman ME; Zaino RJ; Ronnett BM
TI - Hormone receptor immunohistochemistry and human papillomavirus in situ hybridization are useful for distinguishing endocervical and endometrial adenocarcinomas.
SO - Am J Surg Pathol 2002 Aug;26(8):998-1006
AD - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
Determining the origin of uterine adenocarcinomas can be difficult in biopsy and curettage specimens because the morphologic spectrum of endocervical and endometrial adenocarcinomas overlaps. In addition, in hysterectomy specimens the primary site is often equivocal for tumors that involve predominantly the lower uterine segment and endocervix and lack identifiable precursor lesions. We assessed the value of immunohistochemistry for estrogen and progesterone receptors and in situ hybridization for human papillomavirus DNA detection in making this clinically relevant distinction. We evaluated a set of 48 adenocarcinomas of unequivocal origin (24 endocervical carcinomas and 24 endometrial endometrioid carcinomas without cervical extension) and then tested seven lower uterine segment/endocervical carcinomas of equivocal origin to determine whether patterns established in the initial set would permit definitive assignment of primary site for the equivocal set. Only one (4.2%) of 24 endocervical carcinomas was positive for both estrogen receptor and progesterone receptor, whereas 18 (75%) of 24 endometrial carcinomas were positive for estrogen receptor and 23 (95.8%) of 24 endometrial carcinomas were positive for progesterone receptor (p <0.001, chi2 test). Human papillomavirus DNA was detected in 16 (66.7%) of 24 endocervical carcinomas and in none of 24 endometrial carcinomas (p <0.001, chi2 test). Of the seven tumors of equivocal origin, five could be definitively classified as either endocervical or endometrial in origin based on their demonstration of a characteristic profile with these assays (either estrogen receptor/progesterone receptor-negative/human papillomavirus-positive, consistent with endocervical origin or estrogen receptor/progesterone receptor-positive/human papillomavirus-negative, consistent with endometrial origin). We conclude that hormone receptor immunohistochemistry and human papillomavirus in situ hybridization are useful for distinguishing endocervical and endometrial adenocarcinomas. The clinical utility of these techniques should be evaluated in studies that include curettage and biopsy specimens.

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