Overexpression of c-met proto-oncogene associated with chromophilic renal cell carcinoma with papillary growth

Abstract

Various genetic changes are involved in human renal cell carcinomas (RCCs). However, the molecular events related to other cytomorphological subtypes of RCC are not well known, apart from the relationship between the von Hippel-Lindau tumour suppressor gene and clear cell subtype RCC. We examined the overexpression of several growth factor receptors immunohistochemically and analyzed their relationship to the cytomorphological characters in 120 cases of RCCs. These receptors included c-met proto-oncogene product (c-MET), epidermal growth factor receptor (EGFR) and transforming growth factor beta receptor II (TGFbetaR). The overexpression of c-MET was detected in all cases (20/20) of the tubulo-papillary growth type and 78.3% (18/23) of chromophilic cell subtype, resulting in a very significant associations between c-MET overexpression and tubulo-papillary growth RCCs (P<0.0001), c-MET and chromophilic subtype RCCs (P<0.0001), and c-MET and EGFR (P<0.0001). EGFR overexpression was significantly associated with the compact growth RCCs (49/89, P<0.0001), clear cell subtype RCCs (P<0.005) and the overexpression of TGFbetaR (P<0.0001). These results strongly suggest a close correlation between the overexpression of c-MET and development of the chromophilic subtype of RCC with papillary growth pattern. EGFR expression is closely related to the pathogenesis of the clear cell subtype of RCC with compact growth pattern. The overexpression of c-MET, EGFR, and TGFbetaR may have roles that are individually significant in the morphogenesis of RCC.

Immunoblot analysis of c-Met expression in human colorectal cancer: Overexpression is associated with advanced stage cancer

“…Previous studies demonstrated that the relationship of c-Met expression with tumor differentiation seems to vary among different tumor types [23,37,38]. In the current study, c-Met protein levels were low in well-differentiated colon cancers compared to moderately or poorly differentiated cancers.…”

Presence of Phosphorylated Hepatocyte Growth Factor Receptor/c-Met Is Associated with Tumor Progression and Survival in Patients with Conventional Renal Cell Carcinoma

“…Evaluation of HGFR/c-Met expression was assessed semiquantitatively according to a previous report (16). Briefly, specimens were considered to be positive when >50% of cancer cells showed higher staining than normal kidney.…”

“…Activating mutations of HGFR/c-Met have been reported in hereditary type 1 papillary carcinoma (4). Although the same mutation is uncommon in sporadic papillary RCC and is not a typical feature of sporadic conventional RCC, overexpression of HGFR/c-Met is frequently observed (15,16) and it causes ligand-independent activation of receptor tyrosine kinases (17,18). Downstream of overexpressed HGFR/c-Met, phosphoinositide 3-kinase activity is increased (18), which may stimulate proliferation, migration, and survival of renal carcinoma cells through c-Akt and p70 S6 kinase (5,6).…”

Comparison of c-met Expression in Ovarian Epithelial Tumors and Normal Epithelia of the Female Reproductive Tract by Quantitative Laser Scan Microscopy

“…4 In renal cell carcinomas, a close correlation was observed between the overexpression of c-met and the chromophilic subtype with a papillary growth pattern. 20 Di Renzo et al 17 found c-met to be most overexpressed in ovarian carcinomas that were differentiated. In the present study, cmet expression was enhanced in most benign tumors and appeared to be maximally overexpressed in differentiated borderline tumors and differentiated ovarian carcinomas.…”