ABSTRACT
Objective:To determine the clinicopathological significance of the DNA methyltransferase 3B (DNMT3B)overexpression in endometrial carcinomas and to evaluate its correlation with hormone re-ceptor status.Methods:Immunohistochemistry was performed to assess the expression of DNMT3B and hormone receptors in 104 endometrial carcinomas.Results:DNMT3B overexpression occurred frequently in endometrioid carcinoma (EC,54.8%)more than in nonendometrioid carcinoma (NEC,30.0%) with statistical significance (P =0.028).Furthermore,there was a trend that EC with worse clinico-pathological variables and shorter survival had a higher DNMT3B expression,and the correlation between DNMT3B and tumor grade reached statistical significance (P =0.019).A negative correlation between DNMT3B and estrogen receptor (ER)or progesterone receptor (PR)expression was found in EC. NMT3B overexpression occurred frequently in the ER or PR negative subgroups (78.9%,86.7%)more than in the positive subgroups (47.7%,47.8%)with statistical significance (P =0.016,P =0.006). In addition,the DNMT3B overexpression increased in tumors with both ER and PR negative expression (92.9%,P =0.002).However,no such correlation was found in NEC (P >0.05).Sequence analyses demonstrated multiple ER and PR binding sites in the promoter regions of DNMT3B gene.Conclusion:This study showed that the expression of DNMT3B in EC and NEC was different.DNMT3B overexpres-sion in EC was associated with the worse clinicopathological variables and might have predictive value. The methylation status of EC and NEC maybe different.In addition,in EC,DNMT3B overexpression negatively correlated with ER or PR expression.In NEC,the correlation between DNMT3B and ER or PR status was not present.
ABSTRACT
Lynch syndrome is an autosomal dominant genetic disease characterized by the early onset of colon cancer, endometrial cancer and other tumors caused by a genetic mutation within DNA mismatch repair (MMR) genes.A small subgroup (approximately 3% -5%) of endometrial cancer and colorectal cancer is related to Lynch syndrome .Identification of these patients in clinical practice will be of great benefit to the relatives and patients themselves .We reported two cases, and reviewed the literature and clinical diagnostic guideline.MMR protein was lost in the tumors.Meanwhile the two cases had different clinicopathological characteristics.Together with the literature, our findings may suggest that the MMR protein expression, associated molecular alterations and clinicopathological features and biological behavior of endometrial cancer and colorectal cancer related to Lynch syndrome are different .Thus the algorithm for detection the patients at highest risk is different .To detect the MMR loss by immunohisto-chemistry is a practicalscreening method.