Nuclear expression of OCT4, a stem cell transcription factor is associated with tumor aggressiveness in renal cell carcinomas and is an independent prognostic factor for worse progression free survival in clear cell renal cell carcinoma

PurposeOCT4 is one of the key embryonic stem cell (ESCs) transcription factors and is involved in the regulation and maintenance of pluripotency. It is among the most useful stem cell markers for cancer stem cell (CSC) identification which represent a population with tumour-initiating, self-renewal, and differentiation potential. This study aimed to evaluate the expression patterns and clinical signiï cance of OCT4 as a stem cell transcription factor in renal cell carcinoma (RCC).MethodsThe nuclear and cytoplasmic expression of OCT4 was examined in 237 well-deï ned renal tumor tissues, including 162 (68.4 %) clear cell renal cell carcinomas (ccRCC), 41(17.3%) papillary renal cell carcinomas (pRCC) and 34 (14.3%) chromophobe renal cell carcinomas (ChRCC), by immunohistochemistry on a tissue microarray(TMA). The association between expression of this marker and clinicopathologic parameters as well as disease specific (DSS) and progression free survival (PFS) were then analyzed.ResultsOCT4 was observed mainly localized to the nucleous of tumor cells (97.9%). Nuclear OCT4 expression were positively correlated with higher stage and worse PFS in RCC (P values respectively 0.049 and P=0.002) and also worse PFS in ccRCC ( P=0.047). According to the Cox regressions, OCT4 nuclear expression was the only risk factor of PFS in patients with ccRCC (P=0.008). Statistically signiï cant difference between the cytoplasmic expression of OCT4 in the different RCC subtypes was observed (P <0.001).There was positive correlations between cytoplasmic expression of OCT4 and higher grade tumors (P<0.001), microvascular invasion (P=0.001) and shorter DSS (P=0.047) in patients with ccRCC. ConclusionBoth nuclear and cytoplasmic expression levels of OCT4 are associated with tumor progression in RCC samples. Moreover nuclear expression of Oct4 is positively correlated with worse PFS and also is an independent prognostic factor in ccRCC as the most prevalent RCC due to its more aggressive tumor behavior. These findings suggest that nuclear expression of OCT4 rather than its cytoplasmic expression can be considered as a prognostic and therapeutic marker for targeted therapy of RCC especially for ccRCC patients.

کلیدواژه ها:

OCT4 ، embryonic stem cell (ESC) ، renal cell carcinoma (RCC) ، cancer stem cell (CSC) ، Tissue microarray (TMA)