Expression of the macrophage colony‐stimulating factor and its receptor in gynecologic malignancies

Recently, hematopoietic growth factors have been implicated in protean nonhematopoietic processes. In the current study, expression of macrophage colony‐stimulating factor (M‐CSF) and its receptor (the c‐fms proto‐oncogene) was investigated in 42 samples of gynecologic tissues. There were 15 samples of normal ovarian and uterine tissue or benign conditions of these organs; 11 samples of primary ovarian cancer tissue; seven samples of metastatic ovarian cancer tissue; and nine samples of primary endometrial cancer tissue. Steady state transcript levels were assessed by Northern Blot analysis. Macrophage colony‐stimulating factor (M‐CSF) expression was not observed in any of the specimens of benign abnormalities or of normal organs; c‐fms expression was detected in two of 15 (13%) of these specimens, albeit at very low levels. In contrast, 14 (78%) of 18 ovarian tumor specimens, and five (55%) of nine endometrial tumor specimens expressed M‐CSF. Similarly, 16 (89%) of 18 ovarian tumor specimens and six (67%) of nine endometrial tumor specimens expressed c‐fms. Most positive malignant tissues (19 [86%] of 22) showed coexpression of M‐CSF and c‐fms. of interest, M‐CSF and c‐fms mRNA were detected in tumor, but not in adjacent normal tissue. Furthermore, M‐CSF and c‐fms transcripts were produced by all metastatic tumors, including two cases in which the corresponding primary tumor from the same patient was negative. Because M‐CSF mediates its effects by binding to its receptor, the increased levels of both these gene products in gynecologic malignancies suggest that an interaction between M‐CSF and c‐fms may participate in the development of ovarian and endometrial carcinomas and especially in progression to the metastatic state.