Expression of cellular apoptosis susceptibility protein in serous ovarian carcinoma: a clinicopathologic and immunohistochemical study.
OBJECTIVE
This study investigated the expression of cellular apoptosis susceptibility protein (CAS) in serous ovarian carcinoma by immunohistochemistry and compared it with topoisomerase IIalpha (topo IIalpha), 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 IIalpha, 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 IIalpha-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 IIalpha, bcl-2, and bcl-x. Other variables indicating outcome were topo IIalpha, 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.
Brustmann
Hermann
H
Department of Pathology, Thermenklinikum, Moedling/Vienna, Austria. ddrbrustmann@hotmail.com
D000951:Antigens, Neoplasm; D017209:Apoptosis / Q000502:physiology; D029563:Cellular Apoptosis Susceptibility Protein / Q000096:biosynthesis*; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism* / Q000473:pathology*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008938:Mitosis / Q000502:physiology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016612:Paraffin Embedding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis
D000951:Antigens, Neoplasm; D029563:Cellular Apoptosis Susceptibility Protein; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases