Clinical and pathologic features of young endometrial cancer patients with loss of mismatch repair expression

Grzankowski, K.S.; Shimizu, David; Kimata, Chieko; Black, Michael A.; Terada, Keith Y.

doi:10.1016/j.ygyno.2012.05.019

Cited by 26 publications

(24 citation statements)

References 10 publications

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“…The incidence of an isolated loss of MSH6 protein expression in our study was 16.4% (11 of 67 patients). The reported incidence of the loss of MSH6 protein expression in young patients with endometrial carcinomas varies greatly in the literature, ranging from 7% for patients diagnosed at less than 60 yr of age to 26% for patients less than 50 yr of age (2,10). MSH6 loss was also the commonest MMR defect in the latter study (10).…”

Section: Discussionmentioning

confidence: 92%

“…Studies have shown that loss of MMR protein expression in endometrial carcinoma is associated with poor prognostic factors, including higher incidence of high-grade histology, FIGO Stage III/IV, deep myometrial invasion, lymphovascular permeation, and lymph node metastasis (2,15,21). These findings were discussed in a recent review article by Garg and Soslow (22).…”

Section: Discussionmentioning

confidence: 99%

“…Some suggested that loss of MMR function is important in the development of endometrial carcinomas in young women and may be associated with distinct tumor characteristics (2,13,14). Others found that loss of MMR expression was associated with highrisk histopathologic profiles such as higher grades and advanced stages (2,13,15). However, a recent metaanalysis did not show any significant association between MMR status and overall survival or diseasefree survival in endometrial carcinomas (16).…”

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confidence: 99%

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The Significance of Mismatch Repair Deficiency in Young Patients With Endometrial Cancer

Chu

Liu

Tam

et al. 2015

International Journal of Gynecological Pathology

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The objective of this study was to identify the tumor characteristics associated with mismatch repair deficiency in young patients with endometrial carcinoma. Young patients (45 yr old or younger) with endometrial carcinoma treated by hysterectomy in our institution between July 2001 and June 2009 were identified. The clinical and pathologic data were obtained by review of clinical records. Among the 122 cases identified, paraffin sections were available in 67 cases for immunohistochemical staining and frozen tissue available in 62 cases for microsatellite instability (MSI) analysis. Both paraffin sections and frozen tissue were available in 36 cases. Among the 67 cases with immunohistochemical staining, 22 (32.8%) showed loss of expression of at least 1 mismatch repair protein. Defective MLH1 or MSH2 expression was associated with poor prognostic factors, including a higher incidence of pelvic lymph nodes metastasis (P=0.018) and higher stage (P=0.022) for MLH1, and an increased risk of lymphovascular permeation (P=0.015) for MSH2. On the contrary, defective MSH6 protein expression was associated with a lower incidence of high-grade tumors (P=0.04). Among the 62 cases with MSI analysis, 12 (19.4%) tumors were classified as microsatellite-high (MSI-H), whereas 2 (3.2%) were classified as microsatellite-low (MSI-L). There was no difference in the pathologic characteristics between MSI-stable and MSI-H tumor. We concluded that defective mismatch repair expression is important in young patients with endometrial carcinoma, with MSH6 protein being most commonly affected. The phenotype resulting from defective MSH6 expression was different from that caused by MLH1 or MSH2 loss.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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The Significance of Mismatch Repair Deficiency in Young Patients With Endometrial Cancer

Chu

Liu

Tam

et al. 2015

International Journal of Gynecological Pathology

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“…11,12,14,29 Lu et al 14 found that a BMI greater than 30 kg/m 2 and a negative family history were highly predictive of not having an LS mutation. The mean BMI for the mutational carriers was 29.2 kg/m 2 compared with 37.5 kg/m 2 for women without a germline mutation.…”

Section: Discussionmentioning

confidence: 99%

“…The mean BMI for the mutational carriers was 29.2 kg/m 2 compared with 37.5 kg/m 2 for women without a germline mutation. The study by Grzankowski et al, 29 utilizing tumor testing for MMR deficiency, found that a BMI greater than 40 kg/m 2 was observed in zero of the patients with MMR deficient tumors compared with 35% of patient with intact MMR. Based on these studies, one would expect to find a low incidence of LSassociated EC in our very obese Hispanic cohort.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Pathologic Features of Hispanic Endometrial Cancer Patients With Loss of Mismatch Repair Expression

Kost

Valente²,

Lynch³

et al. 2016

Int J Gynecol Cancer

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The prevalence of molecular findings consistent with LS was at least as high as other populations of varied geography, race, and ethnicity. We found no reliable factors to include body mass index, family history, synchronous tumors, or pathologic tumor features to serve as triage markers for which ECs should be screened for MMR protein loss. Our findings support a recommendation for universal screening of ECs utilizing 2-antibody testing with MLH1 promoter methylation testing as indicated up to 60 years or older. Our recommendations should be generalizable to other Hispanic populations in the Southern United States.

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Female Hormonal Factors and the Risk of Endometrial Cancer in Lynch Syndrome

Dashti

Chau

Ouakrim

et al. 2015

JAMA

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IMPORTANCE Apart from hysterectomy, there is no consensus recommendation for reducing endometrial cancer risk for women with a mismatch repair gene mutation (Lynch syndrome).OBJECTIVE To investigate the association between hormonal factors and endometrial cancer risk in Lynch syndrome. DESIGN, SETTING, AND PARTICIPANTSA retrospective cohort study included 1128 women with a mismatch repair gene mutation identified from the Colon Cancer Family Registry. Data were analyzed with a weighted cohort approach. Participants were recruited between 1997 and 2012 from centers across the United States, Australia, Canada, and New Zealand.EXPOSURES Age at menarche, first and last live birth, and menopause; number of live births; hormonal contraceptive use; and postmenopausal hormone use. MAIN OUTCOMES AND MEASURES Self-reported diagnosis of endometrial cancer.RESULTS Endometrial cancer was diagnosed in 133 women (incidence rate per 100 person-years, 0.29; 95% CI, 0.24 to 0.34). Later age at menarche, parity (Ն1 live births), and hormonal contraceptive use (Ն1 year) were associated with a lower risk of endometrial cancer. No. (%) of Women Incidence Hazard Ratio (95% CI) With Available Data Diagnosed With Endometrial Cancer Incidence per 100 Person-Years Difference (95% CI) Age at menarche ≥13 Years 639 70 (11) 0.27 −0.04 (−0.15 to 0.05) 0.70 (0.44 to 1.11) <13 Years (reference) 454 57 (12.6) 0.31 Risk per year 0.85 (0.73 to 0.99) Parity ≥1 Live births 815 88 (10.8) 0.25 −0.18 (−0.32 to −0.04) 0.21 (0.10 to 0.42) Nulliparous (reference) 278 40 (14.4) 0.43 Hormonal contraceptive use ≥1 Year 803 70 (8.7) 0.22 −0.23 (−0.36 to −0.11) 0.39 (0.23 to 0.64) <1 Year (reference) 297 57 (19.2) 0.45 Risk per year 0.93 (0.89 to 0.97)There was no statistically significant association between endometrial cancer and age at first and last live birth, age at menopause, and postmenopausal hormone use. CONCLUSIONS AND RELEVANCEFor women with a mismatch repair gene mutation, some endogenous and exogenous hormonal factors were associated with a lower risk of endometrial cancer. These directions and strengths of associations were similar to those for the general population. If replicated, these findings suggest that women with a mismatch repair gene mutation may be counseled like the general population in regard to hormonal influences on endometrial cancer risk.

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Clinical and pathologic features of young endometrial cancer patients with loss of mismatch repair expression

Cited by 26 publications

References 10 publications

The Significance of Mismatch Repair Deficiency in Young Patients With Endometrial Cancer

The Significance of Mismatch Repair Deficiency in Young Patients With Endometrial Cancer

Clinical and Pathologic Features of Hispanic Endometrial Cancer Patients With Loss of Mismatch Repair Expression

Female Hormonal Factors and the Risk of Endometrial Cancer in Lynch Syndrome

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