Immunohistochemical detection of telomerase (hTERT) and c-kit in serous ovarian neoplasia: a clinicopathological study
Department of Pathology, Thermenklinikum, Moedling/Vienna, Austria
AIM: This study investigated the immunohistochemical expression of telomerase (hTERT) and c-kit in a cohort of serous ovarian carcinomas and to related it to clinicopathologic variables. METHODS: Formalin-fixed, paraffin-embedded archival tissue sections of 10 benign serous cystadenomas (SC), 10 serous neoplasms of low malignant potential (LMP), and 41 serous ovarian carcinomas (SCA) were immunostained with mouse monoclonal antibodies to the catalytic unit of telomerase hTERT and c-kit oncoprotein (Novocastra) utilizing the Vectastain Universal Elite ABC kit. Immunostaining was scored semiquantitatively with regard to approximate percentage of positive tumor cells (<10%, 10% to 50%, >50%) and relative immunostaining intensity (1+, 2+, 3+). Finally, three groups of negative or weak, moderate and strong immunostaining were established. Statistical analysis was done applying the chi-square test for tumor grade and FIGO stage and the log-rank test to compare Kaplan-Meier survival curves. RESULTS: There was no immunoreactivity for hTERT and c-kit in the benign SC. In LMP, seven out of 10 tumors displayed strong nuclear hTERT immunoreactivity; no immunostaining was observed for c-kit. In SCA, hTERT immunoreactivity was nuclear and cytoplasmic. C-kit staining was cytoplasmic and membraneous. Six tumors (14%) were stained only weakly for hTERT, 17 (42%) displayed moderate, and 18 (44%) strong immunoreactivity. For c-kit, 11 tumors (27%) were determined as negative or weak, 19 tumors (46%) stained moderately, and 11 SCA (27%) showed strong staining qualities. hTERT immunostaining was significantly related with grade (P=0,0192), but not with FIGO stage (P=0,3445). In contrast, significant relations were calculated for c-kit immunoreactivity and grade (P=0,0008) as well as FIGO stage (P=0,0247). Regarding prognosis, hTERT immunoreactivity indicated poor outcome (P=0,0477); c-kit expression did not contribute prognostic information (P=0,1145). CONCLUSIONS. Nuclear hTERT immunoreactivity seems to be an early event in serous ovarian neoplasia; nuclear and cytoplasmic staining may indicate poor outcome. In contrast, c-kit immunoreactivity is restricted to SCA, related with high tumor grade and stage, but not related with outcome in this study.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in oral session 797 (Manifestations of cancer).