Lack of expression of c-KIT in ovarian cancers is associated with poor prognosis

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Abstract
The c-KIT protooncogene encodes a tyrosine kinase receptor, KIT, that is expressed in many normal and cancerous tissues. In this study, we have examined the expression of c-KIT and its ligand, stem cell factor (SCF), in human epithelial ovarian tumors, in normal ovaries and in cultured ovarian surface epithelium (OSE). Cultured cells, normal tissues and tumors were analyzed by Northern and Western blot analyses, reverse transcription-polymerase chain reaction and immunohistochemistry. Normal OSE expressed SCF, but not c-KIT; however, epithelial invaginations and inclusion cysts often expressed KIT protein. Of 15 benign ovarian tumors and tumors of low malignant potential, 87% expressed c-KIT, and 92% of these co-expressed SCF, suggesting the possibility of autocrine growth regulation. Of 35 malignant ovarian cancers, 71% expressed c-KIT (92% co-expressed SCF), with a trend for decreased c-KIT expression in advanced stage disease. Of 34 patients with malignant tumors for whom follow-up information was available (median follow-up time of 24 months), 9 had tumors that did not express c-KIT, 8 (89%) of whom have died and the remaining 1 has recurrent disease. Of the 25 patients with tumors expressing c-KIT, 56% are still alive. Eight of the patients have no evidence of disease and all had KIT-expressing tumors. Statistical analysis indicated that patients whose tumors did not express c-KIT had a significantly shorter (p < 0.05) disease-free survival time than patients who had KIT-expressing tumors. Our results suggest that c-KIT may play a role in early ovarian tumorigenesis, and that loss of c-KIT expression is associated with poor prognosis.