The Impact of C-kit and Ki-67 Expression on Patients Prognosis in Advanced Ovarian Serous Carcinoma

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Abstract
The transmembrane-tyrosine-kinase receptor, c-kit, is involved in cell differentiation and has been found to be expressed in normal human cell types and solid tumors. This study was designed to investigate the effects of c-kit expression on: 1) tumor proliferation and apoptosis, and 2) survival in patients with high-grade advanced stage ovarian serous carcinoma (OSC). We identified 118 patients with high-grade advanced stage OSC from our files. Clinical data, including demographics and overall survival, were collected. Immunohistochemical panel consisting of c-kit, ki-67, p53, and bcl-2 was performed. C-kit was categorized as positive if any cytoplasmic or membranous staining pattern was identified. Correlation between c-kit expression and the other markers was performed. Survival analysis was performed using COX proportional hazards regression and Kaplan-Meier test. Of 118 cases, 25 (21.2%) expressed c-kit. Of 93 c-kit-negative tumors, 87.1% had a high proliferation index. High p53 and bcl-2 expression was identified in 96 (81.4%) and 59 (50%) cases respectively. No significant statistical correlation was identified between c-kit and apoptosis markers. Tumors lacking c-kit expression showed a trend toward having high proliferation index, but this did not achieve statistical significance (p = 0.07). Of the seven variables included in the multivariate survival analysis, only c-kit (odds ratio, 2.12; 95% confidence interval, 08-4.17; p = 0.02) and ki-67 (odds ratio, 1.9; 95% confidence interval, 1.1-3.1; p = 0.03) showed an independent statistically significant impact on survival. High-grade advanced stage OSC lacking c-kit expression correlates with poor outcome. Interestingly, cases lacking c-kit expression also showed a trend to have high proliferation index.