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NCI CANCERLIT® Search: Endometrial Cancer - September 2001
Last Modified: November 1, 2001

Table of Contents

CancerMail from the National Cancer Institute

1
UI - 21342262
AU - Archer DF
TI - The effect of the duration of progestin use on the occurrence of endometrial cancer in postmenopausal women.
SO - Menopause 2001 Jul-Aug;8(4):245-51
AD - Department of Obstetrics and Gynecology, and Clinical Research Center, Eastern Virginia Medical School, Norfolk, Virginia, USA. archerdf@evms.edu
OBJECTIVE: Women who have ever used estrogen replacement therapy (ERT), even at a low dose, have an increased incidence of endometrial cancer. The addition of a progestin to ERT reduces the incidence of endometrial cancer. The duration of progestin administration is more important than the dose. DESIGN: A MEDLINE review of the literature was performed using the search terms endometrial cancer, epidemiology, and hormone replacement therapy (HRT). RESULTS: Women who have ever used ERT have an increased incidence of endometrial cancer. The use of HRT for more than 5 years, with a progestin use of <10 days per cycle, has a relative risk = 1.8. Continuous combined HRT, or sequential or cyclic HRT with >10 days of progestin per cycle, appears to decrease the incidence of endometrial cancer to that found in nonusers of HRT. CONCLUSIONS: The use of HRT in postmenopausal women with a uterus reduces the incidence of endometrial cancer. The duration of progestin administration should be 14 days or more per cycle based on recent epidemiologic data.

2
UI - 21376163
AU - Anacak Y; Yalman D; Ozsaran Z; Haydaroglu A
TI - Late radiation effects to the rectum and bladder in gynecologic cancer patients: the comparison of LENT/SOMA and RTOG/EORTC late-effects scoring systems.
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1107-12
AD - Department of Radiation Oncology, Ege University Faculty of Medicine, Izmir, Turkey. yanacak@hotmail.com
PURPOSE: To test the correlation of LENT/SOMA and RTOG/EORTC late-effect scales for rectum and bladder, 116 cases with gynecologic malignancies that were treated with radiotherapy were assessed with both scales. METHODS AND MATERIALS: All cases had been treated at least 6 months before the date of assessment with external beam radiotherapy (50--54 Gy to midline) and 1--2 fractions of HDR brachytherapy (2 x 8.5 Gy to point-A for 32 inoperable cases; 1 x 9.25 Gy to 5--9 mm from the ovoid surface for 84 postoperative cases). The patients were questioned with both scales, and the correlation between the two scales was analyzed by Spearman's rho (rank correlation) test. RESULTS: There were 64 cases with uterine cervix carcinoma and 52 cases with endometrium carcinoma, The overall (external + brachy) doses to ICRU points were 57.8 +/- 3.8 Gy for rectum and 59.3 +/- 4.9 Gy for bladder. The statistical analysis of LENT/SOMA and RTOG/EORTC scales revealed a very good correlation for rectum (r = 0.81; p < 0.01) and a good correlation for bladder (r = 0.72; p < 0.01). CONCLUSION: The LENT/SOMA system is a further step on the reporting of late radiation effects. Some modifications will improve its precision, and multicentric randomized studies are needed to test its validity.

3
UI - 21376167
AU - Mundt AJ; McBride R; Rotmensch J; Waggoner SE; Yamada SD; Connell PP
TI - Significant pelvic recurrence in high-risk pathologic stage I--IV endometrial carcinoma patients after adjuvant chemotherapy alone: implications for adjuvant radiation therapy.
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1145-53
AD - Department of Radiation and Cellular Oncology, Section of Gynecologic Oncology, University of Chicago Hospitals, Chicago, IL 60637, USA. mundt@rover.uchicago.edu
OBJECTIVE: To evaluate the risk of pelvic recurrence (PVR) in high-risk pathologic Stage I--IV endometrial carcinoma patients after adjuvant chemotherapy alone. METHODS: Between 1992 and 1998, 43 high-risk endometrial cancer patients received adjuvant chemotherapy. All patients underwent primary surgery consisting of total abdominal hysterectomy and bilateral salpingo-oophorectomy. No patients received preoperative radiation therapy (RT). Regional lymph nodes and peritoneal cytology were sampled in 62.8% and 83.7% of cases, respectively. Most patients had Stage III--IV disease (83.7%) or unfavorable histology tumors (74.4%). None had evidence of extra-abdominal disease. All patients received 4-6 cycles of chemotherapy as the sole adjuvant therapy, consisting primarily of cisplatin and doxorubicin. Recurrent disease sites were divided into pelvic (vaginal, nonvaginal) and extrapelvic (para-aortic, upper abdomen, liver, and extra-abdominal). Median follow-up was 27 months (range, 2--96 months). RESULTS: Twenty-nine women (67.4%) relapsed. Seventeen (39.5%) recurred in the pelvis and 23 (55.5%) in extrapelvic sites. The 3-year actuarial PVR rate was 46.5%. The most significant factors correlated with PVR were cervical involvement (CI) (p = 0.01) and adnexal (p = 0.05) involvement. Of the 17 women who developed a PVR, 8 relapsed in the vagina, 3 in the nonvaginal pelvis, and 6 in both. The 3-year vaginal and nonvaginal PVR rates were 37.8% and 26%, respectively. The most significant factor correlated with vaginal PVR was CI (p = 0.0007). Deep myometrial invasion (p = 0.02) and lymph nodal involvement (p = 0.03) were both correlated with nonvaginal PVR. Nine of the 29 relapsed patients (31%) developed PVR as their only (6) or first site (3) of recurrence. Factors associated with a higher rate of PVR (as the first or only site) were CI and Stage I--II disease. CONCLUSIONS: PVR is common in high-risk pathologic Stage I-IV endometrial cancer patients after adjuvant chemotherapy alone. These results support the continued use of locoregional RT in patients undergoing adjuvant chemotherapy. Further studies are needed to test the addition of chemotherapy to locoregional RT.

4
UI - 21376168
AU - Mundt AJ; Murphy KT; Rotmensch J; Waggoner SE; Yamada SD; Connell PP
TI - Surgery and postoperative radiation therapy in FIGO Stage IIIC endometrial carcinoma.
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1154-60
AD - Department of Radiation and Cellular Oncology, Section of Gynecologic Oncology, University of Chicago Hospitals, Chicago, IL 60637, USA. mundt@rover.uchicago.edu
OBJECTIVE: To determine the outcome, pattern(s) of failure, and optimal treatment volume in Stage IIIC endometrial carcinoma patients treated with surgery and postoperative radiation therapy (RT). METHODS: Between 1983 and 1998, 30 Stage IIIC endometrial carcinoma patients were treated with primary surgery and postoperative RT at the University of Chicago. All underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, sampling of pelvic lymph nodes (PLN), and peritoneal cytology. All were noted to have PLN involvement. Para-aortic lymph nodes (PALN) were sampled in 26 cases, and were positive in 14 cases (54%). Twenty women received whole-pelvic RT (WPRT) and 10 (WPRT), plus paraortic RT (extended-field RT, EFRT). One EFRT patient also underwent concomitant whole-abdominal RT (WART). Adjuvant vaginal brachytherapy (VB) was delivered in 10, chemotherapy in 5, and hormonal therapy in 7 patients. RESULTS: At a median follow-up of 32 months, the actuarial 5-year disease-free and cause-specific survivals of the entire group were 33.9% and 55.8%, respectively. Overall, 16 women (53%) relapsed. Sites of failure included the pelvis (23%), abdomen (13%), PALN (13%), and distant (40%). Of the 7 pelvic failures, 4 were vaginal (3 vaginal only). Patients treated with VB had a trend to a lower vaginal recurrence rate (0/10 vs. 4/20, p = 0.12) than those not receiving VB. All 4 PALN failures were in women treated with WPRT (2 negative, 1 unsampled, and 1 positive PALN). None of the 10 EFRT patients (2 negative, 8 positive PALN) recurred in the PALN. No patient developed an isolated abdominal recurrence. Two patients developed significant RT sequelae: chronic diarrhea in 1 patient treated with WPRT and VB, and small bowel obstruction in 1 patient treated with EFRT. CONCLUSION: FIGO Stage IIIC disease comprises a small percentage of endometrial carcinoma patients but carries a poor prognosis. Our failure pattern suggests that the optimal adjuvant RT volume is EFRT, even in women with negative PALN sampling. VB should also be administered to improve local control. The low rate of abdominal recurrence does not support the routine use of WART in these women. Given the predominance of failure in distant sites, attention should be focused on the development of systemic chemotherapy protocols.

5
UI - 21395061
AU - Shaarawy M; El-Sharkawy SA
TI - Biomarkers of intrinsic angiogenic and anti-angiogenic activity in patients with endometrial hyperplasia and endometrial cancer.
SO - Acta Oncol 2001;40(4):513-8
AD - Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Egypt.
Serum vascular endothelial growth factor (VEGF) and endostatin were determined in postmenopausal women, including 72 with endometrial cancer, 27 with endometrial hyperplasia and 30 healthy controls. Serum VEGF levels in endometrial hyperplasia (142+/-18 ng/ml, mean +/- SE) and endometrial cancer stages I (291+/-22), II (623+/-68) and stage III-IV (1527+/-119) were significantly higher than the mean for controls (12+/-1.6). Serum endostatin levels in endometrial hyperplasia (149+/-19 ng/ml), endometrial cancer stages I (320+/-41), II (644+/-86) and stage III-IV (1253+/-114) were also significantly higher than the mean for controls (13+/-2.4). Elevated values of VEGF above the non-malignant level were encountered in 7% (stage I), 37% (stage II) and 100% (stage III-IV) of endometrial cancers. The corresponding figures for endostatin were 37%, 59 and 100%, respectively. These results demonstrate that the circulating levels of both markers correlated with tumor stage and apparently tumor burden. Serum VEGF and endostatin levels decreased significantly after treatment, followed by marked elevations at clinical relapse. The VEGF endostatin ratio was higher in the advanced stages ( > 1.0) than in the early stages of endometrial carcinoma (< 1.0). indicating that the balance of angiogenic stimulators and inhibitors may regulate metastasis and access tumor progression.

6
UI - 21396384
AU - Peiro G; Diebold J; Mayr D; Baretton GB; Kimmig R; Schmidt M; Lohrs U
TI - Prognostic relevance of hMLH1, hMSH2, and BAX protein expression in endometrial carcinoma.
SO - Mod Pathol 2001 Aug;14(8):777-83
AD - Institute of Pathology, Ludwig-Maximilians University Munich, Thalkirchnerstr. 36, D-80337 Munich, Germany.
Endometrial carcinoma is the most common gynecologic malignancy in perimenopausal and postmenopausal women. A role of mismatch repair genes, like hMLH1 and hMSH2 in their pathogenesis, has been suggested. Loss of their function leads to the accumulation of replication errors (mutator phenotype), which are responsible for further mutations in genes with microsatellite sequences in their coding region, such as Bax. We analyzed the expression of hMLH1, hMSH2, and Bax genes in 89 formalin-fixed paraffin-embedded endometrial carcinomas. The immunostains were scored with regard to percentage of positive tumor cells (0%, <10%, 10 to 50%, >50%), and relative staining intensity (1+, 2+, 3+). The staining results were correlated with clinicopathologic features and survival. Loss of hMSH2 expression (0% positive cells) was observed in 1.1% (1/89) of the tumors; loss of hMLH1 was seen in 12.4% (11/89) of the cases, particularly in endometrioid tumors with mucinous differentation (5/11; 45%; P =.03). No significant association was found between the immunoscores and grade, stage criteria of the International Federation of Obstetrics and Gynecology (FIGO), or age of the patients. Among 11 tumors with loss of Bax expression (12.4%), 4 had also loss of hMLH1 (4/11; 36.4%; P =.017). In multivariate analysis (Cox model), significantly longer survival was found for patients with tumors in FIGO Stage I-II (P <.0001), endometrioid type (P =.001), low grade (P =.001), and absence of hMLH1 expression (P =.027). Our results suggest that loss of function of hMLH1 and Bax occur in a subgroup of endometrial carcinoma. In addition to the classical prognostic factors, absence of hMLH1 expression is associated with better outcome of patients.

7
UI - 21397959
AU - Bhat KP; Pezzuto JM
TI - Resveratrol exhibits cytostatic and antiestrogenic properties with human endometrial adenocarcinoma (Ishikawa) cells.
SO - Cancer Res 2001 Aug 15;61(16):6137-44
AD - Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Trans-3,4',5-trihydroxystilbene (resveratrol), a polyphenolic compound found in the human diet, was reported recently to serve as an estrogen agonist with cultured MCF-7 cells transfected with estrogen response element-luciferase reporter plasmids. As currently shown, treatment of cultured human endometrial adenocarcinoma (Ishikawa) cells with resveratrol (concentrations as high as 10 microM) did not significantly increase the levels of an estrogen-inducible marker enzyme, alkaline phosphatase. To the contrary, when alkaline phosphatase was induced by treatment with 1 nM of 17beta-estradiol (E(2)), resveratrol exhibited a dose-dependent decrease in activity (IC(50) = 2.3 microM). Furthermore, when Ishikawa cells were treated with resveratrol as a single agent, estrogen-inducible progesterone receptor (PR) was not enhanced, and PR expression induced by treatment with E(2) was inhibited by resveratrol in a dose-dependent fashion at both the mRNA and protein levels. In addition, resveratrol mediated suppression of a functional activity of PR as demonstrated by down-regulation of alpha(1)-integrin expression induced by E(2) plus progesterone. With transient transfection experiments conducted with Ishikawa cells, antiestrogenic effects were confirmed by dose-dependent inhibition of E(2)-induced estrogen response element-luciferase transcriptional activity. Because resveratrol antagonized estrogenic effects in Ishikawa cells, competitive binding analyses were performed to examine the potential of displacing [(3)H]E(2) from human estrogen receptor (ER). Resveratrol showed no discernable activity with ER-alpha, but with ER-beta, E(2) was displaced with an IC(50) of 125 microM. However, mRNA and protein expression of ER-alpha but not ER-beta were suppressed by resveratrol in Ishikawa cells, in the concentration range of 5-15 microM. In addition, in the presence or absence of E(2), resveratrol inhibited Ishikawa cell proliferation in a time-dependent manner with cells accumulating in the S phase of the cycle < or =48 h. This effect was reversible. Analysis of some critical cell cycle proteins revealed a specific increase in expression of cyclins A and E but a decrease in cyclin-dependent kinase 2. These data suggest resveratrol exerts an antiproliferative effect in Ishikawa cells, and the effect may be mediated by both estrogen-dependent and -independent mechanisms.

8
UI - 21379830
AU - Noci I; Borri P; Bonfirraro G; Chieffi O; Arcangeli A; Cherubini A; Dabizzi S; Buccoliero AM; Paglierani M; Taddei GL
TI - Longstanding survival without cancer progression in a patient affected by endometrial carcinoma treated primarily with leuprolide.
SO - Br J Cancer 2001 Aug 3;85(3):333-6
AD - Department of Gynaecology, Perinatal Medicine and Human Reproduction, University of Florence, viale G. B. Morgagni 85, 50134, Firenze, Italy.
We report here a case of a patient affected by endometrial cancer and treated primarily with leuprolide, the surgical approach being unfeasible due to her compromised conditions. The therapy was continued for more than 6 years, and no progression of the disease was observed. During this period, some histological and immunohistochemical evaluations of the tumour (morphology, grading, proliferation and apoptotic index, E-cadherin expression) were performed. Furthermore, the expression of m-RNA for luteinizing-hormone releasing hormone (LHRH) receptors was determined. The results showed a discrepancy between some biological parameters of the tumour and its clinical characteristics. In fact, despite features suggestive of a progression of the cancer (such as the increase of both tumour grading and proliferating capacity (MIB-1), and a fall in the reparative process (appearance of mutated p53, reduced expression of both bcl-2 and c-erb-2) being detected, neither local invasion nor metastatic lesions were clinically observed. This discrepancy might be due to the maintenance of high levels of E-cadhezin. Moreover, since this tumour was shown to express mRNA for LHRH receptors, new evidence is provided about the favourable impact of LHRH analogue treatment in patients affected by endometrial cancer. Copyright 2001 Cancer Research Campaign.

9
UI - 21413066
AU - Touboul E; Belkacemi Y; Buffat L; Deniaud-Alexandre E; Lefranc JP; Lhuillier P; Uzan S; Jannet D; Uzan M; Antoine M; Ginesty C; Ganansia V; Jamali M; Milliez J; Blondon J; Schlienger M
TI - [Endometrial adenocarcinoma treated with combined radiotherapy and surgery: 437 cases]
SO - Cancer Radiother 2001 Aug;5(4):425-44
AD - Service d'oncologie-radiotherapie, centre des tumeurs, hopital Tenon, 4, rue de la Chine, 75020 Paris, France.
PURPOSE: To identify prognostic factors and treatment toxicity in a series of operable endometrial adenocarcinomas. PATIENTS AND METHODS: Between November 1971 and October 1992, 437 patients (pts) with endometrial carcinoma, staged according to the 1988 FIGO staging system, underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy without (n = 140) or with (n = 297) pelvic lymph node dissection. The chronology of RT was not randomized and depended on the usual practices of the surgical teams. Group I: 79 pts received preoperative uterovaginal brachytherapy (mean total dose [MD]: 57 Gy). Group II: 358 pts received postoperative RT (196 pts received vaginal brachytherapy alone [MD: 50 Gy], 158 pts had external beam pelvis RT [EPRT] [MD: 46 Gy over 5 weeks] followed by vaginal brachytherapy [MD: 17 Gy], and 4 pts had EPRT alone [MD: 46 Gy over 5 weeks]). The mean follow-up was 128 months. RESULTS: The 10-year disease-free survival rate was 86%. From 57 recurrences, 12 were isolated locoregionally. Multivariate analysis showed that independent factors decreasing the probability of disease-free survival were: histologic type (clear cell carcinoma, p = 0.038), largest histologic tumor diameter > 3 cm (p = 0.015), histologic grade (p = 0.008), myometrial invasion > 1/2 (p = 0.0055), and 1988 FIGO staging system (p = 9.10(-8)). In group II, the addition of EPRT did not seem to improve locoregional control. The postoperative complication rate was 7%. The independent factors increasing the risk of postoperative complications were FIGO stage (p = 0.02) and pelvic lymph node dissection (p = 0.011). The 10-year rate for grade 3 and 4 late radiation complications according to the LENT-SOMA scoring system was 3.1%. EPRT independently increased the 10-year rate for grade 3 and 4 late radiation complications (R.R.: 5.6, p = 0.0096). CONCLUSION: EPRT increases the risk of late radiation complications. After surgical and histopathologic staging with pelvic lymph node dissection, in a subgroup of intermediate risk patients (stage IA grade 3, IB-C and II), postoperative vaginal brachytherapy alone is probably sufficient to obtain a good therapeutic index. Results for patients with stage III tumor are not satisfactory.

10
UI - 21410097
AU - Ito H; Nakayama H; Noda K; Mitsuda A; Kameda Y; Kato H
TI - A case of lung metastasis from endometrial adenoacanthoma 17 years after initial treatment.
SO - Jpn J Clin Oncol 2001 Jul;31(7):337-40
AD - Division of Thoracic Surgery, Kanagawa Cancer Center, Yokohama, Japan. JZA01742@nifty.com
In March 1982, a 60-old woman presented with an International Federation of Gynecology and Obstetrics grade 1, stage Ib endometrial adenoacanthoma, histological subtype of endometrial carcinoma. The patient underwent radical hysterectomy and was followed up for 10 years, without disease. In August 1998, an abnormal shadow in the right lung was suggested on a chest X-ray film at her routine health check-up and she came to our hospital for further evaluation. A thin-section computed tomographic scan of the chest suggested a malignant lung tumor, but the diagnosis remained tentative. Open biopsy was recommended, but the patient refused and was followed up on an outpatient basis. In November 1999, a thin-section computed tomographic scan of the chest revealed a slightly enlarged tumor and laboratory examination showed a high serum progastrin-releasing peptide concentration of 90.7 pg/ml. We performed partial resection of right upper lobe with video-assisted thoracic surgery. Pathological examination confirmed the lung tumor had metastasized from endometrial adenoacanthoma. Immunohistochemical stainings of estrogen receptor and progesterone receptor were positive both in the primary and lung tumor, only in the component of adenocarcinoma. After surgery, the serum progastrin-releasing peptide concentration remained unchanged. The patient is currently alive and free of disease.

11
UI - 21254384
AU - Glaeser M; Floetotto T; Hanstein B; Beckmann MW; Niederacher D
TI - Gene amplification and expression of the steroid receptor coactivator SRC3 (AIB1) in sporadic breast and endometrial carcinomas.
SO - Horm Metab Res 2001 Mar;33(3):121-6
AD - Department of Gynecology and Obstetrics, Heinrich-Heine-University, Duesseldorf, Germany.
Steroid receptor coactivator 3 (SRC3) functions as a coactivator for nuclear receptor mediated transcriptional activation. It binds to nuclear receptors in a ligand-dependent fashion and recruits other factors such as CBP and p300 to the transactivation complex. Due to its function as activator of nuclear receptors, overexpression of SRC3 might enhance their effects. Gene amplification is a common mechanism that causes overexpression, already described for oncogenes like c-erbB2, c-myc and int2. In this study, SRC3 gene amplification and expression levels were analyzed in 127 sporadic breast carcinomas, 30 endometrial carcinomas and different cell lines (MCF7, HeLa, Ishikawa, T47D, BT-20, SK-BR-3, HEC-1a, RL 95-2, OVCAR3 and A-431). To determine gene amplification and mRNA expression levels, quantitative differential PCR and RT-PCR were performed in combination with fluorescent DNA technology. Gene amplification was not found in any of the breast and endometrial carcinomas, but was found in the carcinoma cell lines MCF7 (10-fold) and HeLa (3-fold). SRC3 overexpression was detected in 13% (3/23) of breast carcinomas and 17% (5/30) of endometrial carcinomas, as well as in MCF7 and HeLa cells. Thus, SRC3 overexpression found in breast and endometrial tumors is not caused by SRC3 gene amplification. A carcinogenic potential provided by SRC3 overexpression has to be elucidated in further studies.

12
UI - 21369413
AU - Purdie DM; Green AC
TI - Epidemiology of endometrial cancer.
SO - Best Pract Res Clin Obstet Gynaecol 2001 Jun;15(3):341-54
AD - Population and Clinical Sciences Division, Queensland Institute of Medical Research, Queensland, 4029, Australia.
Endometrial cancer is the commonest gynaecological cancer mostly affecting women in the post-menopausal age group. Rates vary worldwide and are highest in white women in Western populations. Some risk factors are related to reproduction, such as early age at menarche, late age at menopause and nulliparity, while others are more directly oestrogen-related, for example, conditions such as the polycystic ovarian syndrome. Use of unopposed oestrogen replacement therapy is associated with an increased risk, and use of the combined oral contraceptive pill is associated with a decreased risk. The relationship between tamoxifen and endometrial cancer is not established. Obesity, diabetes and hypertension increase the risk of endometrial cancer while smoking, low-fat diets and physical exercise appear to decrease the risk; all of these possibly exert their effects by various indirect influences on oestrogen levels, thus influencing the level of stimulation of the target endometrial epithelium. Copyright 2001 Harcourt Publishers Ltd.

13
UI - 21369414
AU - Lalloo F; Evans G
TI - Molecular genetics and endometrial cancer.
SO - Best Pract Res Clin Obstet Gynaecol 2001 Jun;15(3):355-63
AD - Department of Clinical Genetics, St Mary's Hospital, Hathersage Rd, Manchester, M13 0JH, UK.
Endometrial cancer is the ninth most common malignancy in females. Inherited forms of this malignancy exist. Mutations in mismatch repair genes result in hereditary non-polyposis colorectal cancer, which confers a lifetime risk of bowel cancer between 60-80% and an endometrial cancer risk of up to 60%. Current screening involves the use of transvaginal ultrasound and hysteroscopy. Genetic testing for mutations in the mismatch repair genes is available, and if a pathogenic change is found within a family, predictive testing becomes available for unaffected family members. If blood samples from family members are unavailable, tumour blocks may be studied to assess microsatellite instability, a feature of mismatch repair gene mutations.While mutations in the mismatch repair genes are found in inherited endometrial cancer they are rarely seen in sporadic cancers. However, there are a range of somatic gene mutations that are currently being studied in order to provide insight into the pathogenesis of endometrial cancer. Copyright 2001 Harcourt Publishers Ltd.

14
UI - 21369415
AU - Neven P; Vergote I
TI - Tamoxifen, screening and new oestrogen receptor modulators.
SO - Best Pract Res Clin Obstet Gynaecol 2001 Jun;15(3):365-80
AD - Department of Obstetrics and Gynaecology, Algemene Kliniek St.-Jan, Broekstraat 104, Brussels, B-1000, Belgium.
Tamoxifen is a selective oestrogen receptor modulator (SERM) with anti-oestrogenic properties in the breast and oestrogenic effects in tissues such as bone and the cardiovascular system. It is an excellent breast cancer drug for all stages of the disease. Its SERM profile makes it a valuable alternative to hormone replacement therapy, especially for women at high risk of breast cancer. Tamoxifen, however, increases the incidence of benign and malignant lesions of the uterus. Secondary prevention of these, early detection and treatment, is feasible but not cost-effective in breast cancer patients because potential endometrial risks do not outweigh beneficial effects in the breast. This may be different in healthy women with an as yet unknown benefit on breast cancer mortality.We review the literature on the importance of tamoxifen's endometrial lesions and balance available evidence on whether and how best to screen them. In a subset of tamoxifen users it seems advisable to assess the uterine cavity prior to intake with a yearly endometrial assessment as pointed out, starting 3 years after initiation of treatment. In most cases there is endometrial thickening on ultrasonographic assessment and additional tests such as hydrosonography or hysteroscopy are required to confirm an empty atrophic uterus as remains the case in most asymptomatic women on tamoxifen.Newer compounds, such as raloxifene, have a similar SERM profile to tamoxifen but are neutral on the uterus. This has recently been proven by 3 years of endometrial follow-up data. Longer endometrial safety will hopefully confirm these early findings. Whether other SERMs in development are better, and which of them is better for the breast, is to be demonstrated in ongoing studies. Copyright 2001 Harcourt Publishers Ltd.

15
UI - 21369416
AU - Symonds I
TI - Ultrasound, hysteroscopy and endometrial biopsy in the investigation of endometrial cancer.
SO - Best Pract Res Clin Obstet Gynaecol 2001 Jun;15(3):381-91
AD - School of Human Development, University of Nottingham Faculty of Health Sciences, Academic Department of Obstetrics and Gynaecology, Derby City General Hospital, Uttoexeter Road, Derby, DE22 3NE, UK.
Over the course of the last two decades hysteroscopy with endometrial biopsy has begun to replace dilation and curettage as the method of choice for the diagnosis of endometrial carcinoma. In the majority of women this can be performed as an outpatient procedure with no loss in diagnostic accuracy. Transvaginal ultrasound measurement of endometrial thickness provides a highly sensitive and less invasive alternative means of assessing the endometrium but has a low positive predictive value for cancer, especially in women taking hormone replacement therapy. The cut-off value used to define normality needs to take into account patient age and ethnic origin. Ultrasound screening may not be suitable for women taking tamoxifen and those with recurrent or late-onset abnormal uterine bleeding. Copyright 2001 Harcourt Publishers Ltd.

16
UI - 21369418
AU - Kitchener HC
TI - Surgery for endometrial cancer: what type and by whom?
SO - Best Pract Res Clin Obstet Gynaecol 2001 Jun;15(3):407-15
AD - Academic Unit of Obstetrics and Gynaecology, St Mary's Hospital, Manchester, Whitworth Park, M13 0JH, UK.
Endometrial cancer has far too long been regarded as a simple disease to treat. As such it has generally remained in the hands of the generalist obstetrician/gynaecologist.In order to optimize the choice of surgery, careful pre-operative evaluation is essential with respect to pathology of a biopsy, radiological assessment of extent of disease and evaluation of fitness for anaesthesia.The standard procedure is a total abdominal hysterectomy and bilateral salpingo-oophorectomy. However, consideration should be given to pelvic lymphadenectomy in high-risk cases. Surgery for high-risk endometrial cancer should be performed by gynaecological oncologists. Copyright 2001 Harcourt Publishers Ltd.

17
UI - 21369419
AU - Koh WJ; Tran AB; Douglas JG; Stelzer KJ
TI - Radiation therapy in endometrial cancer.
SO - Best Pract Res Clin Obstet Gynaecol 2001 Jun;15(3):417-32
AD - Department of Radiation Oncology, University of Washington Medical Center, Seattle, WA 98195, USA.
The role of radiation in endometrial cancer, especially in the adjuvant setting, is controversial. Factors that influence radiotherapy recommendations include surgical considerations, pathological findings, potential sites of disease recurrence and the practice philosophies of the individual physician. It has been demonstrated that adjuvant radiotherapy following primary surgery significantly improves pelvic tumour control, but has no measurable impact on overall survival in an unselected patient population. Studies to date have been hampered by the inclusion of patients with a wide spectrum of prognostic features; this may decrease the likelihood of observing greater benefit in discriminate subsets at higher risk of relapse. Further trials are required to define clinical prognosis more precisely and to investigate the role of radiation in higher-risk patients. In the meantime, we propose guidelines for radiotherapy in endometrial cancer which serve as bases for discussion and collaboration among physicians and as platforms for future study and progress. Copyright 2001 Harcourt Publishers Ltd.

18
UI - 21369420
AU - Trope C; Kristensen GB; Abeler VM
TI - Clear-cell and papillary serous cancer: treatment options.
SO - Best Pract Res Clin Obstet Gynaecol 2001 Jun;15(3):433-46
AD - Department of Gynecologic Oncology, The University Clinic, The Norvegian Radium Hospital, Montebello, N-0310, Oslo, Norway.
Clear-cell carcinoma (CCC) and serous papillary carcinoma of the endometrium (UPSC) are rare subtypes of endometrial carcinoma (10%). The histological diagnosis can be made on the dilation and curettage specimens in both types in a very high percentage of the cases. This is important in the planning of treatment. CCC and UPSC are associated with about 50% of all relapses occurring in endometrial carcinoma, and the 5-year survival rate is, on average, 42% and 27% respectively. Surgico-pathological stage, age, and vessel invasion are independent prognostic factors for both groups. The recurrence rate is extremely high, and the most frequent extra-pelvic sites of relapse are the upper abdomen, lungs and liver. Stage Ia patients treated with complete surgical staging alone have a low risk of relapse and need not be offered adjuvant systemic therapy or pelvic radiation. The treatment of patients with CCC and UPSC stage Ib, Ic, II and III should include radical debulking surgery and some form of adjuvant therapy, but it is not clear which type is most effective. Adjuvant pelvic radiotherapy plus intracavitary radiotherapy is usually given in early-stage disease and pelvic radio therapy/or whole abdomen irradiation plus adjuvant systemic chemotherapy (PAC) in advanced disease. However, we are urgently waiting for a large prospective randomized study to compare both modalities. Paclitaxel, alone or in combination, is currently being tested in phase II studies. Copyright 2001 Harcourt Publishers Ltd.

19
UI - 21369421
AU - Steer C; Harper P
TI - Is there any place for cytotoxic chemotherapy in endometrial cancer?
SO - Best Pract Res Clin Obstet Gynaecol 2001 Jun;15(3):447-67
AD - Department of Medical Oncology, 3rd Floor, Thomas Guy House, Guy's Hospital, St Thomas Street, London, SE1 9RT, UK.
Cytotoxic chemotherapy has an established role in the treatment of many solid tumours that are considered to be incurable with any modern treatment method. Such treatment may result in an improvement in quality of life without influencing overall survival. In this chapter the evidence to support the use of chemotherapy in patients with advanced or recurrent endometrial adenocarcinoma is reviewed. The most effective single agent and combination treatments are outlined. Although evidence from randomized trials is limited, combination chemotherapy can lead to response rates of over 40% in patients with advanced disease. The role of chemotherapy as adjuvant treatment in patients with early-stage disease is less well defined and this treatment is not recommended outside a clinical trial. The role of chemotherapy for treatment of the aggressive histological variant, uterine papillary serous carcinoma is also discussed. Copyright 2001 Harcourt Publishers Ltd.

20
UI - 21369422
AU - Podczaski E; Mortel R
TI - Hormonal treatment of endometrial cancer: past, present and future.
SO - Best Pract Res Clin Obstet Gynaecol 2001 Jun;15(3):469-89
AD - Department of Obstetrics and Gynecology, Penn State College of Medicine, The Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033-2390, USA.
The concept that hormonal therapy may be useful in the treatment of endometrial cancer antedated the pharmaceutical availability of progestational compounds. By 1959, initial studies demonstrated the ability of progestins to reverse endometrial hyperplasias. Thereafter, progestins and other hormonal agents have been used in various roles as treatment for endometrial cancers. This chapter reviews the use of hormonal agents for the treatment of primary and metastatic/recurrent endometrial cancer, as well as such treatment in an adjuvant setting. Major problems in enhancing the efficacy of endocrine therapy of cancers arising from hormonally responsive tissues are also considered. The regulations of steroid-hormone receptor expression in endometrial and breast cancers continues to be an active area of research interest. Copyright 2001 Harcourt Publishers Ltd.

21
UI - 21423697
AU - Lo KW; Cheung TH; Yim SF; Chung TK
TI - Preoperative hysteroscopic assessment of cervical invasion by endometrial carcinoma: a retrospective study.
SO - Gynecol Oncol 2001 Aug;82(2):279-82
AD - Division of Gynecologic Oncology, The Chinese University of Hong Kong, Shatin, Hong Kong.
OBJECTIVE: The aim of this study was to evaluate the efficacy of hysteroscopy, using normal saline (NS) or carbon dioxide (CO2) as the distention medium, in assessing tumor invasion of the uterine cervix by endometrial carcinoma. METHODS: A retrospective study was conducted in 200 consecutive patients with endometrial carcinoma diagnosed from 1993 to 2000. Prior to definitive surgical treatment, hysteroscopy was performed using either NS or CO2 as the distention medium to determine whether the tumor had spread to the cervix. The uterine specimens obtained after hysterectomies were cut open for gross examination. Tumor invasion of the cervix as determined by hysteroscopy and gross examinations was compared with the pathological findings. RESULTS: Tumor invasion of the cervix was found in 41 (20.5%) cases on pathological examination. Hysteroscopy has an accuracy of 92.5% (185/200), a sensitivity of 68.3% (28/41), and a specificity of 98.7% (157/159), with a PPV of 93.3% (28/30) and a NPV of 92.4% (157/170) in determining cervical involvement. Assessment by gross inspection had 93.0% (186/200) accuracy, 68.3% (28/41) sensitivity, 99.4% (158/159) specificity, 96.6% (28/29) PPV, and 92.4% (158/171) NPV. There was no significant difference between the two assessment methods. When the results of hysteroscopy performed with different distention mediums were compared, the use of NS had a higher accuracy in determining tumor spread to the cervix (96.8% vs 88.7%, P = 0.03) and NPV (96.4% vs 88.4%, P < 0.05) than the use of CO2. CONCLUSIONS: Hysteroscopic assessment and gross examination of the uterine specimen had similar efficacy in detecting cervical invasion by endometrial carcinoma. Hysteroscopic examination using NS is more accurate than that which uses CO2. Copyright 2001 Academic Press.

22
UI - 21423707
AU - Ashman JB; Connell PP; Yamada D; Rotmensch J; Waggoner SE; Mundt AJ
TI - Outcome of endometrial carcinoma patients with involvement of the uterine serosa.
SO - Gynecol Oncol 2001 Aug;82(2):338-43
AD - Department of Radiation and Cellular Oncology, University of Chicago Hospitals, Illinois, 60637, USA.
OBJECTIVE: The goal of this work was to evaluate the outcome of endometrial carcinoma patients undergoing primary surgery who have serosal involvement (SI). METHODS: Between 1980 and 1998, 562 women underwent primary surgery for endometrial cancer at the University of Chicago. Thirty-nine were noted to have SI. FIGO stages were IIIA (19), IIIB (1), IIIC (7), and IV (12). Of the 19 IIIA patients, 15 had solitary SI. Twenty-six patients received pelvic radiation therapy (RT) with or without vaginal brachytherapy (VB). One patient received whole-abdomen radiation therapy, and 13, adjuvant chemotherapy. Solitary SI patients received pelvic RT with or without VB as their sole adjuvant therapy. Disease-free survivals (DFSs) were estimated using the method of Kaplan and Meier and prognostic factors were analyzed by the log-rank test. RESULTS: With a median follow-up of 30.3 months, the 5-year actuarial DFS of the entire group was 28.9%. Factors correlated with disease recurrence included tumor stage (P = 0.003) and lymph node involvement (P = 0.04). In addition, patients with solitary SI had a better 5-year DFS (41.5% vs 20%, P = 0.04) than patients with SI plus other extrauterine sites. Relapse occurred in 23 women overall and in 7 of 15 solitary SI patients. The most common site of disease recurrence was distant both in the entire group and in the solitary SI patients. While abdominal recurrences were common in the entire group, they were infrequent in solitary SI patients. CONCLUSION: Endometrial carcinoma patients with SI have a high rate of relapse and a poor outcome. Even when patients have extrauterine disease limited to SI, the outcome is relatively unfavorable. Nonetheless, our results demonstrate the need to distinguish patients with solitary SI and those with SI plus other extrauterine disease sites. Copyright 2001 Academic Press.

23
UI - 21423714
AU - Fanning J
TI - Long-term survival of intermediate risk endometrial cancer (stage IG3, IC, II) treated with full lymphadenectomy and brachytherapy without teletherapy.
SO - Gynecol Oncol 2001 Aug;82(2):371-4
AD - Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Medical College of Ohio, Toledo, Ohio 43614-5809, USA.
OBJECTIVES: The aim of this study was to determine long-term survival and late complications of intermediate risk endometrial cancer (Stage IG3, IC, and II) treated with full lymphadenectomy and brachytherapy without teletherapy. METHODS: Two-hundred sixty-five consecutive patients underwent surgical staging for endometrial cancer consisting of hysterectomy, oophorectomy, and bilateral pelvic and periaortic lymphadenectomy. Sixty-six patients had intermediate risk endometrial cancer (Stage IG3, IC, and II) and received postoperative brachytherapy without teletherapy. Mean age was 68 years and mean weight was 188 lb. Seventy-seven percent had associated medical illness. RESULTS: At a mean follow-up of 4.4 years, Kaplan-Meier estimated 5-year progression free survival is 97%. Two patients (3%) developed distant recurrence (abdomen, lungs) with no vaginal or pelvic recurrence. Major complications occurred in 6% of patients. CONCLUSIONS: Complete lymphadenectomy with brachytherapy without teletherapy for intermediate risk endometrial cancer results in excellent progression-free survival and minimal major morbidity. Copyright 2001 Academic Press.

24
UI - 21423715
AU - McMeekin DS; Lashbrook D; Gold M; Scribner DR; Kamelle S; Tillmanns TD; Mannel R
TI - Nodal distribution and its significance in FIGO stage IIIc endometrial cancer.
SO - Gynecol Oncol 2001 Aug;82(2):375-9
AD - Department of Obstetrics-Gynecology, University of Oklahoma, Oklahoma City, Oklahoma 73190, USA.
OBJECTIVE: The aim of this study was to describe the distribution of nodal disease in FIGO Stage IIIc endometrial cancer (EC) and to evaluate whether nodal distribution is related to recurrence and survival. METHODS: Charts from EC patients with FIGO Stage IIIc disease from 1989 to 1998 were abstracted for clinicopathologic data, pelvic (PLN) and para-aortic (PALN) nodal involvement, number of positive/removed nodes, and extranodal disease spread. Patterns of nodal distribution were evaluated for site of first recurrence and survival. Associations between variables were tested by chi(2) and Wilcoxon rank sums. Survival analyses were performed by the Kaplan-Meier method. RESULTS: Of 607 EC patients evaluated, 47 were identified with FIGO Stage IIIc disease. All 47 patients underwent hysterectomy and PLN sampling, and 42/47 had PALN sampling. The median number of PLN removed was 16 (range 2-35), and the median number of PALN was 7 (0-18). Stage IIIc disease was defined by positive PLN alone in 43%, positive PLN and PALN in 40%, and positive PALN alone in 17%. Positive peritoneal cytology and/or adnexal metastasis were present in 12 patients. Only 1/12 of these patients had isolated positive PLN whereas 11/12 had positive PALN (P = 0.007). An increasing number of positive PLN was associated with PALN metastasis (P = 0.0001), and of the 10 patients with bilateral PLN involvement, 9/10 also had positive PALN (P = 0.001). Sites of first recurrence were similar regardless of whether PALN were positive. At a median follow-up of 37 months, the 3-year survival estimate was 70% for patients with positive PALN versus 87% for those with isolated PLN disease (P = 0.22). For all patients neither the total number of positive PLN nor the total number of PLN or PALN removed was associated with survival. CONCLUSIONS: PALN involvement is common in patients with FIGO Stage IIIc endometrial cancer, suggesting that PLN sampling alone may result in underdiagnosis of disease. Patients with positive PALN had more extensive disease, but survival and patterns of failure were not significantly different from those with disease confined to PLN, suggesting that lymph node dissection may have a therapeutic role. Copyright 2001 Academic Press.

25
UI - 21423717
AU - Maluf FC; Sabbatini P; Schwartz L; Xia J; Aghajanian C
TI - Endometrial stromal sarcoma: objective response to letrozole.
SO - Gynecol Oncol 2001 Aug;82(2):384-8
AD - The Developmental Chemotherapy Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA.
BACKGROUND: Low-grade endometrial stromal sarcoma is generally an indolent tumor rich in estrogen and progesterone receptors. Objective responses to hormonal therapy, most commonly with megestrol acetate, have been reported. CASE: The patient is a 51-year-old woman who presented with low-grade endometrial stromal sarcoma confined to the uterus in 1991 and was treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy. Approximately 5 years later, the patient had recurrent pelvic disease treated with radiation therapy, followed by an attempt at resection. She was treated with megestrol acetate during the period she received radiation therapy with poor tolerance. Tamoxifen was then given with no tumor response. Megestrol acetate was restarted with progression of disease in the pelvis and abdomen. Letrozole was then given at a daily dose of 2.5 mg with partial response for a duration of 9 months. CONCLUSION: Letrozole at a daily dose of 2.5 mg may be effective in low-grade endometrial stromal sarcoma with positive estrogen receptors. Copyright 2001 Academic Press.

26
UI - 21423720
AU - Parker R; Lanvin D; Gilks B; Miller D
TI - Spontaneous regression of stage IV clear cell carcinoma of the endometrium in a patient with essential thrombocytosis.
SO - Gynecol Oncol 2001 Aug;82(2):395-9
AD - Department of Pathology, Vancouver Hospital and British Columbia Cancer Agency, Vancouver, British Columbia, V5Z 1M9, Canada.
OBJECTIVE: The aim of this study was to document a case of advanced stage clear cell carcinoma of the endometrium which underwent spontaneous regression (SR) and comment on the possible contribution of the patient's thrombocytosis. CASE REPORT: A 73-year-old woman with essential thrombocytosis presented with vaginal bleeding. Imaging demonstrated a complex uterine mass, a 4-cm infrarenal mass, and a 5-cm subumbilical mass. Biopsy of the subumbilical mass revealed adenocarcinoma, and endometrial curettage revealed extensively necrotic clear cell endometrial carcinoma. At hysterectomy 5 weeks later, the infrarenal and subumbilical masses were not identified. The endometrial tumor was almost completely necrotic. She received no adjuvant therapy and remains disease-free 6 years later. Interestingly, her platelet-lowering agent (hydroxyurea) was discontinued shortly before, and her platelet count was significantly elevated at the time of her presentation with endometrial carcinoma. CONCLUSION: This report documents a rare case of SR of advanced endometrial carcinoma, and we speculate that increased circulating platelets were a major contributing factor. Copyright 2001 Academic Press.

27
UI - 21423724
AU - Petereit DG; Frederickson H
TI - Regarding Ng et al.: Defining the role of adjuvant radiotherapy for high-risk stage I endometrial patients.
SO - Gynecol Oncol 2001 Aug;82(2):407-9

28
UI - 21422027
AU - Ridgeway JJ; Pettigrew C; Gallup DG; Burke JJ; Weber FH
TI - Recurrent ascites and pleural effusions after surgery for early-stage endometrial adenocarcinoma.
SO - South Med J 2001 Jul;94(7):738-40
AD - Department of Obstetrics and Gynecology, Memorial Health University Medical Center, Savannah, GA 31403, USA.
A case of massive postoperative ascites in a woman treated for endometrial cancer is reported. A workup for typical causes of ascites yielded negative results, prompting a more detailed analysis of the patient's condition. Hypothyroidism was discovered. After correction of the hypothyroidism, the ascites slowly resolved. Since myxedema is an uncommon cause of ascites, this is usually a diagnosis of exclusion. However, hypothyroidism must be ruled out to prevent unnecessary and possibly inappropriate treatments for ascites.

29
UI - 20043550
AU - Orvieto R; Bar-Hava I; Dicker D; Bar J; Ben-Rafael Z; Neri A
TI - Endometrial polyps during menopause: characterization and significance.
SO - Acta Obstet Gynecol Scand 1999 Nov;78(10):883-6
AD - Department of Obstetrics and Gynecology, Rabin Medical Center, Petah Tiqva, Israel.
BACKGROUND: To characterize postmenopausal women with endometrial polyps and to evaluate their significance. METHODS: The study population included all consecutive postmenopausal patients with a diagnosis of endometrial polyp, treated at our center over a two-year period. Demographic, medical and gynecological data were assessed with regard to the endometrial histologic findings. RESULTS: Of the 146 eligible patients, 15 had endometrial hyperplasia (four with atypia); there were no cases of endometrial carcinoma. The 20 patients (13.7%) using hormone replacement therapy had a significantly highe

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