Pathologic features of endometrial carcinoma associated with HNPCC

Abstract

BACKGROUNDEndometrial carcinoma is a common malignancy in hereditary nonpolyposis colorectal carcinoma (HNPCC). Like colon carcinoma, endometrial carcinoma is diagnosed at an earlier age in women with HNPCC. In contrast to colon carcinoma, the pathologic features of endometrial carcinoma in HNPCC have not been studied in detail. It was the purpose of this study to pathologically characterize a series of HNPCC associated endometrial carcinomas.METHODSFifty women with HNPCC and endometrial carcinoma were analyzed from four different hereditary cancer registries. H&E stained slides and pathology reports were reviewed for clinically important pathologic features of endometrial carcinoma. These results were compared with those for two different groups of sporadic endometrial carcinoma – women younger than age 50 years (n = 42) and women of all ages with tumors demonstrating microsatellite instability (MSI‐high) secondary to methylation of MLH1 (n = 26).RESULTSNearly one‐fourth of HNPCC patients in this study had endometrial tumors with pathologic features that would require adjuvant therapy after hysterectomy. There was a trend toward the HNPCC patients having more nonendometrioid tumors; all of these patients were carriers of MSH2 mutations. Such nonendometrioid tumors were extremely rare in the MLH1 methylated group. A subset of MLH1 methylated sporadic tumors demonstrated a unique, ‘undifferentiated’ histology that was not observed in HNPCC or the young group.CONCLUSIONData suggest a genotype–phenotype relation in which microsatellite instability resulting from MLH1 methylation is almost exclusively associated with classical or ‘undifferentiated’ endometrioid tumors, whereas microsatellite instability secondary to MSH2 mutation can result in a more variable histologic spectrum of endometrial carcinoma. Cancer 2006. © 2005 American Cancer Society.

ZEB1 overexpression associated with E-cadherin and microRNA-200 downregulation is characteristic of undifferentiated endometrial carcinoma

“…1 These morphological features suggest that some undifferentiated carcinomas derive from endometrioid endometrial carcinomas and that molecular changes characteristic of endometrioid tumors are likely to be found in undifferentiated endometrial carcinomas. In this regard, we confirmed previous observations 1,17 by demonstrating that the presence of DNA mismatch repair abnormalities was characteristic of undifferentiated endometrial carcinomas. This molecular alteration has been observed in 20-30% of EECs in a different series 18 and it was present in nearly 40% of undifferentiated endometrial carcinomas in the present series.…”

“…Although this series comprised 16 tumors previously analyzed, the frequency of mismatch repair abnormalities in new cases (40% or 2/5) was similar to that of the prior study (37% or 6/16). Mismatch abnormalities in undifferentiated endometrial carcinomas were first reported in sporadic tumors 17 and it was subsequently observed that undifferentiated endometrial carcinomas can also occur in Lynch syndrome. 1 In the present series, one patient showed loss of MSH2 and MSH6 expression in her undifferentiated endometrial carcinoma and is considered to be a presumptive Lynch syndrome patient.…”

Comparison of lifestyle, hormonal and medical factors in women with sporadic and Lynch syndrome-associated endometrial cancer: A retrospective case-case study

“…According to these studies, risk factors are partially shared in sporadic and hereditary EC, since the BMI appeared not to have an effect on EC risk, although parity, longer use of hormonal contraceptives and a later age at menarche reduced the risk of EC in LS women (19,20). It has been suggested that LS women have more non-endometrioid tumors compared with sporadic patients, which could at least partly explain certain of the differences in the reported risk factor profiles (19)(20)(21). LS mutation carriers in the present study used hormonal contraceptives more frequently than non-carriers.…”

Cost‐effectiveness analysis of prevention strategies for gynecologic cancers in Lynch syndrome

“…OCPs decrease endometrial and ovarian cancer risks in the general population by approximately 50%, [34][35][36][37][38][39][40][41][42][43] and progestin intrauterine devices may reverse hyperplasia and early endometrial cancer. 44,45 Because Lynch syndrome-associated gynecologic cancers appear to be similar to sporadic cases, 4,46 these chemoprevention strategies may be beneficial with less adverse effect on quality of life than prophylactic surgery. Our group recently completed accrual to an endometrial cancer chemoprevention study comparing OCPs and Depo-Provera for women with Lynch syndrome, and data analysis currently is ongoing.…”