Tyrosine kinase receptor RON and its ligand MSP in Merkel cell carcinoma.

The RON gene, encoding the tyrosine-kinase receptor for macrophage-stimulating protein (MSP), is involved in a range of neoplastic processes. However, no aberration in RON or MSP has been identified in Merkel cell carcinoma (MCC). We investigated the RON signaling pathway in MCC. Fourteen cases of MCC were tested for the expression of RON and its ligand, MSP, using reverse transcription PCR (RT-PCR) and immunohistochemistry. The mutation of RON was also examined. RT-PCR identified transcription of both RON and MSP in all nine cases that were available for the examination. Immunohistochemistry showed the expression of RON (9/14 cases) and MSP (9/14 cases). Six cases out of 14 were positive for both RON and MSP. Normal Merkel cells were negative for RON and MSP expression. Missense mutation in the tyrosine kinase region of RON was detected in one of the 14 cases, and the case showed expression of RON. Transcription of RON and MSP was observed in MCC, and a considerable number of MCC cases expressed both RON and MSP, while Merkel cells do not express these molecules. The results suggest that RON signaling seems to play at least some role in the pathogenesis of MCC.