Activated extracellular signal-regulated kinase is an independent prognostic factor in clinically confined renal cell carcinoma.
BACKGROUND
Extracellular signal-regulated kinase (ERK) promotes proliferation, metastasis, and poor survival in cancers of the breast, lung, and liver. Advanced localized renal cell carcinoma (RCC) is extraordinarily treatment resistant and has high recurrence rates despite surgery. Limited data exist regarding the prognostic significance of activated (phosphorylated) ERK in RCC. The authors hypothesized that activated ERK (pERK) promotes disease progression and metastasis in localized RCC and may be of value as a biomarker to predict disease recurrence.


METHODS
The expression profile of pERK was examined by immunocytochemistry using a tissue microarray constructed from 174 drug treatment-naive patients who had undergone radical nephrectomy for localized RCC. Levels of tumor-cell specific pERK were scored and correlated with clinicopathologic parameters of RCC and disease-free survival.


RESULTS
Immunostaining for pERK was present in 36% of all RCCs, with a predominance found in the clear cell histologic subtype. High expression was associated with increased tumor size, increased TNM stage, and vascular invasion. Patients with pERK-positive tumors had a mean disease-free survival of 4.19 years, compared with 6.38 years for patients with pERK-negative tumors (P<.001). Cox regression models revealed pERK to be a significant independent predictor of disease-free survival, with a hazards score of 2.9 (P<.001), a value similar to tumor grade (hazards ratio, 3.01; P<.001).


CONCLUSIONS
Expression of pERK is an independent prognostic factor in RCC that is associated with advanced and aggressive pathologic features of renal tumors and predicts the onset of metastasis in patients with localized disease.
Campbell
Lee
L
Welsh School Of Pharmacy, Department of Pathology, Cardiff University, Cardiff, United Kingdom.
Nuttall
Rosa
R
Griffiths
David
D
Gumbleton
Mark
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000201:enzymology*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D011379:Prognosis; D046888:Tissue Array Analysis
D015415:Biomarkers; D019950:Mitogen-Activated Protein Kinase 1