RCC-Ma loss predicts poor survival and metastatic risk in clear cell renal cell carcinoma

Abstract

Background With the increasing number of renal cell carcinoma subtypes and implications for prognosis and therapy, correct classification of renal masses remains a challenging issue. Clear cell renal cell carcinoma (ccRCC) is a tumor with an immunoprofile that often does not follow paradigmatic rules. Thus, the aim of this study was to analyze the heterogeneity of immunohistochemical staining patterns in ccRCC regarding patient prognosis. Methods The study cohort consisted of 727 ccRCC patients with surgical treatment between 1995 and 2006 and with comprehensive clinicopathological information and follow-up data. Only 1.6 % of patients received modern targeted therapy after surgery. The patients were stratified analogue to the Leibovich Risk Score (LRS). A tissue microarray was immunohistochemically stained for vimentin, CAIX, CD10, RCC-Ma, AMACR, CK7 and CD117. The expression in the tumor tissue was semiquantitatively scored and tested for association with clinicopathological tumor features and patient survival. Results Loss of RCC-Ma was an independent prognostic biomarker for disease specific survival (p = 0.01) and associated with a higher risk of developing metastasis in the intermediate risk group of the LRS as well as aggressive tumor features, such as higher tumor grade and stage, metastasis and necrosis. The other analyzed immunohistochemical biomarkers had no impact on patient prognosis. Conclusion As a predictor of poor survival and metastatic risk, RCC-Ma is likely to be a valuable contributor to the risk stratification in ccRCC patients. Moreover, this study cohort provides a valuable resource for investigations on the natural, therapy-naive clinical course of the disease and can serve as a reference for other study collectives, including patients treated with up-to-date targeted therapies.