HER2 Expression in Peritoneal Dissemination of High-Grade Serous Ovarian Carcinoma: A Comparative Study of Immunohistochemical Reactivity Using Four HER2 Antibodies

Abstract

Most high-grade serous ovarian carcinomas (HGSOCs) involving the peritoneum are aggressive. Epidermal growth factor receptor 2 (HER2) is aberrantly activated in a variety of solid cancers. The HER2 status of a tumor is based on cytoplasmic membrane staining of an intracellular domain (ICD)-specific HER2 antibody. We compared four anti-HER2 antibodies in an immunohistochemical study of HGSOC with peritoneal dissemination. HER2 expression was assessed in peritoneal disseminated HGSOC specimens from 38 patients by immunohistochemistry using four different anti-HER2 antibodies (an ICD antibody (clone A0485), an extracellular domain (ECD) antibody (clone SP3), and two antibodies recognizing HER2 phosphorylated at tyrosine 877 or 1248 (pHER2Y877 and pHER2Y1248)). HER2 gene amplification was accessed by chromogenic in situ hybridization (CISH). The antibodies showed HER2 positivity as follows: 31.6% of cases (12/38) with A0485, 26.3% (10/38) with SP3, 7.9% (3/38) with pHER2Y877, and 21.1% (8/38) with pHER2Y1248. Fifteen out of thirty-eight (39.5%) cases were positive for at least one of the four HER2 antibodies. HER2 gene amplification was detected in 3/19 cases. All four HER2 antibodies could be used for patient selection for anti-HER2 therapies. These findings raise the possibility of anti-HER2 therapeutic strategies for HGSOC with peritoneal dissemination.