Adipophilin as prognostic biomarker in clear cell renal cell carcinoma

Abstract

// Yuri Tolkach 1, * , Christine Lüders 1, * , Sebastian Meller 1 , Klaus Jung 2, 3 , Carsten Stephan 2, 3 , Glen Kristiansen 1 1 Institute for Pathology, University Hospital Bonn, Bonn, Germany 2 Berlin Institute of Urologic Research, Berlin, Germany 3 Department of Urology, Charité, Universitätsmedizin Berlin, Berlin, Germany * These authors have contributed equally to this work Correspondence to: Glen Kristiansen, email: glen.kristiansen@ukb.uni-bonn.de Keywords: renal cell carcinoma, clear cell, adipophilin, perilipin 2, PLIN2 Received: December 12, 2016      Accepted: January 27, 2017      Published: February 23, 2017 ABSTRACT Objective: To study the expression of adipophilin ( PLIN2 ), a lipid storage-associated cell protein, in different subtypes of renal cell cancer and to elucidate its prognostic value. Materials and Methods: Two-hundred-seventy-five patients with renal cell carcinoma (RCC) were included in this study. Immunohistochemistry with a polyclonal antibody to adipophilin was used on the tissue microarray (formalin-fixed, paraffin-embedded tissue) for detection of adipophilin. Median follow-up time was 91 (range 1-159) months in the whole cohort and 100 (1-159) months for patients with clear-cell RCC. Additional validation for adipophilin was performed using publicly available gene expression data for clear cell RCC from The Cancer Genome Atlas (TCGA). Results: Adipophilin expression was detected in 14.3% of papillary RCC, in 0% of chromophobe RCC and in 58.7% of clear-cell RCC in the cytoplasm or at the membrane. Only membrane expression was correlated with other clinical parameters (pT-stage, pN-stage, R-status, sex) and showed a prognostic significance in univariate analysis with regard to overall survival of patients with clear cell subtype (HR 2.90, 95% CI 1.55-5.42, p=0.001), which failed significance on multivariate analysis. mRNA expression of PLIN2 on TCGA data using best selected cut-off was prognostically significant in both univariate (HR 1.76, 95% CI 1.28-2.42, p = 0.0005) and multivariate analyses (HR 1.46, 95% CI 1.05-2.04, p = 0.0257). Conclusions: Adipophilin is a novel and still understudied prognostic biomarker in clear cell renal cell carcinoma which deserves further study.