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.