MET Expression in Sporadic Renal Cell Carcinomas

Abstract

Although germline mutations of met proto-oncogene on human chromosome 7q31-34 have been known as useful molecular markers of hereditary papillary renal cell carcinoma (RCC), the expression of MET, a product of met proto-oncogene, has not been fully studied in sporadic RCC, along with its clinical significance. We investigated the expression of MET by immunohistochemistry in 182 cases of renal neoplasm encompassing 145 RCC, 25 urothelial carcinomas of renal pelvis, and 12 oncocytomas. MET was diffusely and strongly expressed in 90% of papillary RCC, all collecting duct carcinomas, and 92% of urothelial carcinomas of renal pelvis. On the contrary, clear cell RCC, chromophobe RCC, and oncocytomas were negative or focally positive for MET expression. In clear cell RCC, MET expression was positively correlated with high nuclear grade, presence of infiltrative growth, tumoral necrosis, papillary architecture, sarcomatoid component, tumoral involvement of the renal pelvis or ureter, involvement of the calyx, and lymphatic invasion. In conclusion, diffuse and strong expression of MET in papillary RCC and collecting duct carcinoma might be helpful in discriminating from the other subtypes of RCC with tubular or papillary growth. In case of MET expression observed in clear cell RCC, it might correlate with those clinicopathological parameters implying aggressive behavior.

MET Is a Potential Target across All Papillary Renal Cell Carcinomas: Result from a Large Molecular Study of pRCC with CGH Array and Matching Gene Expression Array

“…Protein expression level was not only higher in RCC tissue than in adjacent paired normal tissue but also significantly higher in papillary than in clear cell subtypes (P < 0.0001). MET protein expression has been reported in up to 90% of pRCC, including both type I and type II in a pathology report from Choi and colleagues (32).…”

Papillary renal cell carcinoma: A review of the current therapeutic landscape

“…A strong MET expression (between 80% and 100%) has been described [30][31][32]. However, Choi et al showed no significant difference in MET over-expression between type 1 and type 2 pRCC [31]. High MET expression has been associated with increasing tumor stage and poor survival [30].…”

Nonclinical Evaluation of the Serum Pharmacodynamic Biomarkers HGF and Shed MET following Dosing with the Anti-MET Monovalent Monoclonal Antibody Onartuzumab

“…Total tumor MET expression, determined by immunohistochemistry (IHC), has been used to identify patients with a worse prognosis in multiple indications (27,(48)(49)(50). The companion diagnostic assay for onartuzumab, CONFiRM c-MET IHC assay using SP44 rabbit monoclonal antibody verified that patients expressing high MET levels (2þ, 3þ) in second-and third-line NSCLC had a worse outcome in the erlotinib control arm (26,27).…”