title: The impact of c-kit and ki-67 expression on patients prognosis in advanced ovarian serous carcinoma.
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.
authors.affiliation: Department of Pathology, Harper University Hospital, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Khalifeh
authors.forename: Adnan R
authors.initials: AR
authors.lastname: Munkarah
authors.forename: Veronica
authors.initials: V
authors.lastname: Schimp
authors.forename: Robert
authors.initials: R
authors.lastname: Morris
authors.forename: W Dwayne
authors.initials: WD
authors.lastname: Lawrence
authors.forename: Rouba
authors.initials: R
authors.lastname: Ali-Fehmi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis* / Q000235:genetics; D012189:Retrospective Studies; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D019009:Proto-Oncogene Proteins c-kit