Expression of cellular apoptosis susceptibility protein in serous ovarian carcinoma: a clinicopathologic and immunohistochemical study

Abstract

Objective. This study investigated the expression of cellular apoptosis susceptibility protein (CAS) in serous ovarian carcinoma by immunohistochemistry and compared it with topoisomerase IIα (topo IIα), bcl-2, bcl-x, the frequency of apoptotic bodies (ABI), mitotic activity, and c-erbB-2 with regard to clinicopathologic variables. Methods. Formalin-fixed, paraffin-embedded archival tissue sections of 10 benign serous cystadenomas, 10 serous neoplasms of low malignant potential (LMP), and 41 serous ovarian carcinomas were immunostained with antibodies to CAS, bcl-x, topo IIα, bcl-2, and c-erbB-2. Immunostaining for CAS, bcl-x, and bcl-2 was scored concerning approximate percentage of positive tumor cells and relative staining intensity. For c-erbB-2, at least 10% of tumor cells had to display membrane staining. Topo IIα-labeling indices were quantitated as the percentage of positively stained nuclei in 1000 tumor cells. ABIs were reported as the number of apoptotic bodies in 1000 tumor cells, mitotic activity as mitotic figures per 10 high power fields. Results. CAS expression was negative in serous cystadenomas and LMP. In contrast, moderate or strong immunostaining was observed in 34 of 41 cases (83%) of serous carcinomas. CAS immunoreactivity was positively related with ABI ( P = 0.0170), mitotic activity ( P < 0.0001), c-erbB-2 ( P = 0.0153), grade ( P = 0.0107), and adverse outcome ( P = 0.0035), but not with FIGO stage, topo IIα, bcl-2, and bcl-x. Other variables indicating outcome were topo IIα, c-erbB-2, and ABI. Conclusions. CAS is frequently upregulated in serous ovarian carcinomas, correlated with apoptosis and mitotic activity, and relevant prognostically. CAS protein expression may serve as a marker of aggressive tumor behavior in serous ovarian carcinomas.