Phosphorylation of ERK1/2 and Prognosis of Clear Cell Renal Cell Carcinoma

Abstract

To evaluate the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) in clear cell renal cell carcinoma (CCRCC) and to investigate its prognostic significance. ERK1/2 activation had been reported in RCC, but little is known about its prognostic significance. We immunohistochemically analyzed phosphorylated ERK1/2 (pERK) expression using tissue microarrays in 328 CCRCC specimens. The percentage of tumor cells showing positive staining was evaluated and classified into 4 categories: 0, 0%; 1+, 1%-10%; 2+, 11%-50%; and 3+, > 50%. For statistical analysis, the cases were subdivided into pERK-low (0 and 1+) and pERK-high (2+ and 3+) expression. Our study showed significantly greater expression of pERK in CCRCC than in non-neoplastic renal parenchyma. pERK-high expression was significantly associated with a low pT category (P = .046). The survival analysis showed a significant association between pERK-high expression and better progression-free survival (P = .014). Furthermore, the prognostic significance of pERK expression was quite different between small CCRCC (size < or = 7 cm) and large CCRCC (size > 7 cm) lesions. In small CCRCC, pERK-high expression correlated significantly with better cancer-specific survival (P = .018) and better progression-free survival (P < .001). However, no correlation was found between pERK expression and survival in large CCRCC. High expression of pERK in CCRCC was associated with a low pT category and showed a longer progression-free survival, especially in small CCRCC. Although the biologic mechanism of the ERK pathway in CCRCC remains unknown, the results of this study suggest that pERK expression is a positive prognosticator for survival in those with small CCRCC.