Evaluation of MTAP immunohistochemistry loss of expression in ovarian serous borderline tumors as a potential marker for prognosis and progression

Introduction: Serous borderline tumors (SBT) are the most common subtype of ovarian borderline tumors with excellent clinical course. However, they can recur or progress to low-grade serous carcinoma (LGSC) in a small proportion of the cases. Beside BRAF and KRAS mutations, copy number alterations (CNA), particularly loss of chromosome 9p21 locus which results in deletion of genes CDKN2A and MTAP, have been suggested to be involved in disease progression. MTAP immunohistochemistry recently has been introduced for mesothelioma as a reliable surrogate marker for the homozygous deletion of chromosome 9p21 locus. Therefore, in the current study, we aimed to evaluate the MTAP loss of expression in serous borderline tumors and low-grade serous carcinomas to identify if it can be used as a marker for prognosis and progression. Method: Eighty-four total cases of ovarian serous lesions, including 21 cases of serous cystadenomas, 21 cases of serous borderline tumors, 12 cases of low-grade serous carcinomas and 30 cases of high-grade serous carcinomas were selected. MTAP immunohistochemistry was performed on the representative blocks and cytoplasmic staining was used for interpretation. The cases were labeled as positive (retained) if MTAP showed cytoplasmic granular staining and negative (loss of expression) if negative cytoplasmic staining was observed in the presence of positive internal control. Result: Ten of 21 cases of serous borderline tumors showed loss of MTAP expression (48%). Among those, 7 cases were bilateral, 2 cases had micropapillary features, one case had supraclavicular and cervical lymph node involvement by serous borderline tumor and 2 cases had progression to low-grade serous carcinoma, including one of micropapillary tumors. Also 8 out of 12 cases of LGSCs showed MTAP loss of expression (66%). Only 4 of 30 cases of high-grade serous carcinomas (13%) and none of the serous cystadenoma cases showed loss of expression of MTAP. Conclusion: To our knowledge, this is the first description of MTAP immunohistochemistry in serous borderline tumors and low-grade serous carcinomas. Our study was limited due to small sample size. However, it showed an association between MTAP loss of expression and adverse clinical behavior in ovarian serous borderline tumors. This supports the role for further investigations in larger series to evaluate the role of MTAP stain as a prognostic marker in these neoplasms.