Clinicopathologic characteristics of double primary endometrial and colorectal cancers in a single institution.

AIM: To investigate the clinicopathologic and genetic correlations between double primary endometrial and colorectal cancer related to Lynch syndrome and to analyze germline mutations in mismatch repair genes in endometrial cancer patients in Korea. METHODS: Thirteen patients diagnosed with pathologically endometrial and colorectal cancer between January 2005 and November 2016 in a single institution were enrolled in the study. The medical records were retrospectively analyzed. The genetic mutational information of endometrial cancer in Korea was retrieved from the literature review. RESULTS: Endometrial cancer was diagnosed first in eight (62%) patients, and one patient was diagnosed with colorectal cancer first. Endometrioid adenocarcinoma was reported in 10 of 13 (77%) endometrial cancer patients. Endometrial cancer was found at the low uterine segment in three patients. Three of four patients had high microsatellite instability. The loss of mismatch repair proteins was confirmed in 7 of 11 cases using immunohistochemistry. Four patients fulfilled clinical criteria based on a family history of cancer. Overall, the incidence of suspected Lynch syndrome was 77% (10/13). Four of them underwent genetic testing and three were found to have a pathogenic germline mutation. A possible founder mutation, c.1757_1758insC in MLH1, was observed in 21 germline mutation information from literature review. CONCLUSION: The present study describes the clinicopathologic data of double primary endometrial and colorectal cancer patients and supports that these patients should undergo closed approach for Lynch syndrome. Moreover, a possible founder mutation in Korean endometrial cancer patients was identified.

Prognostic significance of Notch 3 gene expression in ovarian serous carcinoma.

The Notch signaling pathway is an important cell signaling system, which regulates cell differentiation, proliferation, and apoptosis, and is aberrantly activated in a wide range of cancer, including ovarian cancers. However, it remains unclear as to whether Notch signaling plays a role in the progression and prognosis of ovarian cancer. We examined the mRNA and protein expression of Notch 3, Jagged 1, and Jagged 2 in 98 ovarian epithelial tumors via real-time PCR and in 175 tumors with immunohistochemical analysis, and then correlated their expression levels with clinicopathological parameters and patient survival. In this study, we detected high levels of Notch3 mRNA and protein expression especially in serous ovarian carcinomas compared to their benign counterparts, accompanied by a positive correlation with the expressions of Jagged 1 and Jagged 2. High levels of Notch 3 mRNA expression (>2-fold than that of benign tumor) were noted in 63% of the serous carcinomas (mean level: 17-fold, P = 0.032). Additionally, Notch 3 protein overexpression was significantly associated with advanced stage (P = 0.0008), lymph node (P = 0.001), and distant metastasis (P = 0.003). Notably, high Notch 3 mRNA and protein expressions were correlated with chemoresistance (P = 0.033) and poor overall survival (P = 0.027, P = 0.042) in these patients. Our results indicate that the Notch 3 signaling pathway is involved in the tumor progression of ovarian serous carcinoma, and higher Notch 3 expression may be an independent poor prognostic factor in this subset of tumors.