Abstract
ObjectiveTo 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 MethodsTwo-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).ResultsAdipophilin 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).ConclusionsAdipophilin is a novel and still understudied prognostic biomarker in clear cell renal cell carcinoma which deserves further study.
Highlights
Kidney cancer is one of the ten most frequently occurring cancers with substantial mortality estimates in Western societies [1]
Adipophilin expression was detected in 14.3% of papillary renal cell carcinoma (RCC), in 0% of chromophobe RCC and in 58.7% of clear-cell RCC in the cytoplasm or at the membrane
Membrane expression was correlated with other clinical parameters 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 The Cancer Genome Atlas (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)
Summary
Kidney cancer is one of the ten most frequently occurring cancers with substantial mortality estimates in Western societies [1]. Adipophilin is one of the important players in lipid metabolism, responsible for storage of lipid droplets in all types of cells [4, 5]. Some recent studies show that many tumors overexpress adipophilin [6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22], especially those with clear cell histology [10, 11]. Several small reports showed that renal cell carcinoma (RCC) cells overexpress adipophilin [10, 11, 23,24,25,26,27] and one major study [24] reported the prognostic role of this biomarker in www.impactjournals.com/oncotarget clear cell subtype on transcript level. An analysis on the protein level was pending, so far
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