The statuses of HER2 expression and mismatch repair in endometrial clear cell carcinoma

Abstract

High-grade endometrial carcinomas (HGEC) are difficult to classify. With the current use of HER2-based therapy in serous carcinoma, a diagnosis of clear cell carcinoma (CCC) has the potential to exclude patients from receiving therapy. Therefore, we examined HER2 expression in our CCC patients. The preparations of 8 patients with CCC who underwent hysterectomy, bilateral salpingo-oophorectomy, and lymph node dissection were re-evaluated. Patients did not have any prior treatment. Histopathologic parameters that were evaluated include cytoplasmic clearing, nuclear atypia, mitotic activity, hobnail architecture, hyalinized cores, hyaline globules, stratification of epithelial lining papillae, or glandular structures, and highly atypical cell layers. Immunohistochemically, HER2, ER, PR, HNF1β, Napsin A, MLH1, MSH2, MSH6 and PMS2 were applied. HER2 staining pattern, ASCO/CAP protocol used for endometrial carcinom was used. HER2 was positive in 3 of our 8 CCC patients (37.5%). While all of our HER2 + cases were Napsin A and HNF1β positive, MMR proteins were intact and ER and PR were negative. Two patients had wild type p53 and 1 patient had aberrant p53 staining. Considering that there is not always a consensus between SC and CCC, even among gynecopathologists, tumor heterogeneity and different tumor components may exist, and while patients may be diagnosed with CCC and benefit from HER2 therapy, there is also a possibility that they may not benefit from the treatment. The fact that 37.5% of our CCC cases were HER2 + is a finding with strong implications for the therapeutic approach. As a result of our study, in patients with CCC, if MMR is intact and ER-PR is negative, regardless of the p53 staining pattern, HER2 testing may be an objective screening method for patients who are likely to benefit from HER-targeted therapy. Consequently, patients with a diagnosis of CCC can be candidates for future clinical trials of HER2-targeted therapy.

Keywords: Clear cell carcinoma; HER2; High-grade endometrial carcinoma; Transtuzumab.