An immunohistochemical and morphological analysis of post-chemotherapy ovarian carcinoma

Abstract

Aims: Traditional management of advanced ovarian carcinoma is surgical debulking followed by chemotherapy; however, there is an increasing tendency for neoadjuvant chemotherapy followed by surgery. The morphology of ovarian carcinoma following chemotherapy often differs markedly from native tumour; it may be difficult to identify residual tumour cells, to confirm that any residual carcinoma is ovarian in origin and to subtype the ovarian carcinoma. We aimed to compare the immunophenotype of post-chemotherapy ovarian carcinomas with that of untreated tumour. Methods and Results: We stained a series of post-chemotherapy ovarian carcinomas (n=16) with a range of antibodies, including markers which are useful in the diagnosis of ovarian carcinoma, especially of serous type, and cell cycle related markers. In 6 cases, pre-chemotherapy core biopsies were also stained; these were all high grade serous carcinomas. Antibodies used in the study were CK7, CA125, WT1, ER, PR, p53, p16, p63 and MIB1. In 8 of the post-treatment cases, there was minimal or no morphological response to chemotherapy and in 8 there was a significant response (there were 2 additional cases where no residual tumour was identified). In all pre-chemotherapy core biopsies, there was diffuse positivity of the tumour cells with CK7, CA125 and WT1. ER, p53 and p16 were diffusely positive in 5, 4 and 3 cases respectively. One case was focally PR positive and all were p63 negative. MIB1 staining was high with all but one case exhibiting a proliferation index of >60%. Post-chemotherapy tumours exhibited a similar immunophenotype with diffuse positivity with CK7 in all cases and with CA125, WT1, ER, p53 and p16 in the majority, an immunophenotype in keeping with a serous carcinoma. All were negative with p63 and all but 2 with PR. The MIB1 proliferation index was lower in those cases exhibiting a significant morphological response. Conclusions: The immunophenotype of post-chemotherapy ovarian carcinomas is very similar to that of native untreated tumours, illustrating that CK7, CA125, WT1, ER, p53 and p16 may be of value in identifying residual tumour cells and in subtyping the neoplasm if a pre-chemotherapy biopsy has not been obtained.