Phosphorylation of ERK1/2 and prognosis of clear cell renal cell carcinoma.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Pathology, Seoul National University, College of Medicine, Seoul, Korea.
Hyun Ju
HJ
Lee
Dong-Il
DI
Kim
Gyeong Hoon
GH
Kang
Cheol
C
Kwak
Ja Hyeon
JH
Ku
Kyung Chul
KC
Moon
D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000401:mortality; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis; D016019:Survival Analysis
D048052:Mitogen-Activated Protein Kinase 3