Lynch Syndrome in patients with clear cell and endometrioid cancers of the ovary

Abstract

Objective Patients with Lynch Syndrome are at an increased risk for a variety of malignancies, including ovarian cancer. Ovarian cancers associated with Lynch Syndrome are predominantly clear cell or endometrioid in histology. Lynch Syndrome is characterized by germline mutations in mismatch repair (MMR) genes. The current study aims to assess the prevalence of loss of MMR expression in patients with endometrioid and clear cell ovarian carcinoma. Methods A retrospective review identified 90 patients with endometrioid and/or clear cell carcinomas. Slides made from tumor tissue microarray blocks were evaluated using immunohistochemical stains with antibodies against MLH1, PMS2, MSH2, and MSH6. Statistical analysis was performed. Results Seven of the 90 cases (7.8%) had loss of MMR expression. The mean age of patients with loss of MMR expression (47 years) was significantly younger than those with retained MMR expression (p = 0.014). Loss of MMR expression was present in 20% of patients under the age of 53 with clear cell or endometrioid cancers. Genetic studies found that 3 of the 5 patients with loss of MMR expression carried mutations consistent with Lynch Syndrome; acquired hypermethylation of MLH1 was noted in one patient. Six of 7 patients (86%) whose tumors lacked MMR expression had synchronous or metachronous primary malignancies, a significantly greater prevalence than those with retained MMR expression (p < 0.001). Conclusion Patients under the age of 53 with clear cell or endometrioid ovarian carcinomas are at a clinically significant risk for loss of MMR expression and Lynch Syndrome; routine screening with immunohistochemical staining should be considered.

The Prevalence and Associated Factors of Microsatellite Instability in Ovarian Epithelial Cancers Detected by Molecular Genetic Studies in a Sample of Iranian Women

“…The wide range was due to differences in study design, number, and type of detector markers and the criteria for the definition of MSI-H (14, 15). However, in the studies using Bethesda panel markers or MSI analysis system, the rate of MMR system defects has been reported at about 10% (CI95% = 6 -14) in ovarian epithelial cancers (16)(17)(18). Therefore, our results are consistent with previous findings regarding the overall rate of MSI in all histological types.…”

Molecular-based classification algorithm for endometrial carcinoma categorizes ovarian endometrioid carcinoma into prognostically significant groups

“…highlight the potential role of p53 as a marker of adverse behavior, independent of traditional parameters such as tumor grade. Defective mismatch repair protein immunohistochemistry has been reported in 10-14% of ovarian endometrioid carcinomas, [30][31][32] similar to the prevalence seen in our cohort (6/72 cases, 8%). Over 50% of MMR-deficient ovarian endometrioid carcinomas have loss of MSH2 and/or MSH6.…”

Long‐term survival of patients with mismatch repair protein‐deficient, high‐stage ovarian clear cell carcinoma

“…Lynch syndrome‐associated and MMR protein‐deficient ovarian carcinomas are most commonly of clear cell or endometrioid subtype although, conversely, only 2–14% of these tumours demonstrate MMR protein deficiency and/or MSI . The current study, albeit restricted specifically to high‐stage CCC, supported these findings, as MMR protein‐deficiency was identified in only two of 32 tumours (6.3%).…”