Clinicopathologic significance of DNA mismatch repair protein defects and endometrial cancer in women 40years of age and younger.

The hereditary basis of endometrial cancer is apparent in young women with endometrial cancer. The objective of this study was to examine risk factors and outcomes in patients 40 years of age and younger with endometrial cancer. We performed a retrospective cohort study of patients aged 40 years or less who were diagnosed with endometrial carcinoma between 1/93 and 5/08. Clinical and pathologic data were extracted from medical records. Paraffin-embedded slides from hysterectomy specimens were obtained and DNA mismatch repair (MMR) immunohistochemistry was performed. Cases were analyzed according to the presence of DNA MMR protein defects. Standard two-sided statistical tests were performed. Of the 56 identified patients, the median age was 36 years (range, 24-40). The majority of the endometrial carcinomas were of endometrioid histology (91%), stage I (71%), and FIGO grade 1 (59%). Abnormal DNA MMR was found in 9 cases (16%). Cases with abnormal DNA MMR had lower body mass index (BMI) (P=0.05), and had a family history suggestive of Lynch syndrome (P=0.001). Tumors were more likely to have advanced stage disease (P<0.001), be high grade (P<0.001), have deep myometrial invasion (P<0.001), and have lymphovascular invasion (P=0.002). Cases with abnormal DNA MMR had significantly worse overall survival (P=0.028) and progression-free survival (P=0.042). Endometrial cancer is rare in women aged 40 years or less. In this group of patients, loss of DNA MMR was associated with lower BMI, worse clinicopathologic factors, and worse outcome. These results may have implications when young women diagnosed with endometrial cancer are counseled regarding prognosis.

Shih KK ，Garg K ，Levine DA ，Kauff ND ，Abu-Rustum NR ，Soslow RA ，Barakat RR ... -  《-》

Endometrial carcinomas in women aged 40 years and younger: tumors associated with loss of DNA mismatch repair proteins comprise a distinct clinicopathologic subset.

Garg K ，Shih K ，Barakat R ，Zhou Q ，Iasonos A ，Soslow RA ... -  《-》

Women 50 years or younger with endometrial cancer: the argument for universal mismatch repair screening and potential for targeted therapeutics.

Ring KL ，Connor EV ，Atkins KA ，Ricketts W ，Kashlan B ，Modesitt SC ... -  《-》

Mismatch repair protein expression in 1049 endometrial carcinomas, associations with body mass index, and other clinicopathologic variables.

Links between obesity, with its attendant estrogen abnormalities, and the endometrial carcinoma (EC) DNA Mismatch Repair Protein (MMR) system have recently been proposed. We investigated relationships between body mass index (BMI) and clinicopathological correlates including MMR expression in a large single institution EC cohort. Clinical and pathological databases from 2007 to 2012 were used to identify consecutive hysterectomy specimens with EC. Univariate and multivariate analyses were used to explore relationships between BMI, age, stage, tumor type and immunohistochemical results for MLH1, PMS2, MSH2 and MSH6. 1049 EC were identified. Overall, BMI was higher amongst women with normal MMR (p=0.002). However, when stratified by age and specific MMR, statistically significant differences localized exclusively to women <50years old with loss of MSH2 and/or MSH6 (p=0.003 and p=0.005 respectively). Higher BMI correlated with endometrioid FIGO 1 and 2 tumors (p<0.001) and with stage 1a (p<0.001). Conversely, MMR abnormalities did not show significant associations with stage (p=0.302) or histologic grade (p=0.097). BMI showed statistically significant associations with MMR expression, tumor grade and stage amongst 1049 consecutive EC. Obesity correlates with lower grade and stage EC. A link between BMI and maintenance of the MMR system is not supported by our data because the only statistically significant association occurred in women <50years old with MSH2 and/or MSH6 abnormalities where Lynch syndrome related cases are expected to cluster.

Joehlin-Price AS ，Perrino CM ，Stephens J ，Backes FJ ，Goodfellow PJ ，Cohn DE ，Suarez AA ... -  《-》

[Lynch syndrome-related endometrial carcinoma].

Pang SJ ，Guo DH 《-》