1041P - Clinical features and frequency of mismatch repair protein deficiency in ovarian clear cell and endometrioid carcinoma patients

Abstract

BackgroundThe rates of mismatch repair (MMR) protein deficiency and microsatellite instability (MSI) in ovarian clear cell (CC) and endometrioid (EM) cancer patients were investigated. The clinical features of CC and EM were also analyzed. MethodsPatients postoperatively diagnosed as CC or EM carcinoma from January 2006 to December 2015 were eligible. Diagnosis of all cases was confirmed by the Central Pathological Review Board. MMR protein was analyzed by IHC using a monoclonal antibody and MSI was examined by a multiplex PCR assay for five microsatellite markers, BAT25, BAT26, NR-21, NR-24, and MONO-27. MLH1 IHC-negative cases were examined for DNA hypermethylation of the MLH1 promoter. ResultsWe enrolled 339 cases consisting of 219CC, 116 EM and 4 mixed type (MT) cases. One case could not be evaluated by IHC. MMR protein deficiency was confirmed in five CC (2.3%), 16 EM (13.9%) and 1MT case (25%). Deficiency was observed in 4 cases for MLH1 and PMS2, in 13 cases for MSH2 and MSH6, in 1 case for MSH2 and PMS2, in 2 cases for MSH6, and in 1 case for PMS2. DNA hypermethylation of the MLH1 promoter was detected in one of the four MLH1 and PMS2 deficiency cases. Three of the 339 cases could not be evaluated by MSI. A high rate of MSI was confirmed in 13 cases (3.9%) and MMR deficiency was detected by IHC in these cases. However, MSI was not detected in the other nine cases where MMR deficiency was detected by IHC. The median age of all 339 cases was 54 (CC 54, EM 51) and that of CC and EM cases with MMR deficiency was 39 and 48 years, respectively. ConclusionsThe rate of MMR deficiency in CC and EM was not high, whereas CC in young women was more frequent. IHC is a more successful screening method of MMR deficiency in ovarian CC and EM compared with MSI detection. The rate of MLH1 promoter hypermethylation (epigenetic MMR deficiency) in ovarian CC and EM was less than that of endometrial cancer. Legal entity responsible for the studyThe author. FundingNational Hospital Organization of Japan. DisclosureThe author has declared no conflicts of interest.