Clinical significance of nuclear and cytoplasmic expression of stemness marker Nanog in different histological subtypes of renal cell carcinoma: A study using tissue microarrays (TMA)

Objective: Nanog is a key transcription factor in self renewal and pluripotency of embryonic stem cells. The aim of this study was to evaluate Nanog expression as a stemnessmarker in Renal Cell Carcinoma (RCC). Methods: The expression of Nanog in RCC specimens was evaluated by immunohistochemistry on a tissue microarray(TMA). Two hundred and thirty-two consecutive patients treated surgically for renal cell carcinoma (RCC) between 2010 and 2015 including 157(70.4%) Clear Cell Renal Cell Carcinoma (ccRCC), 37(16.6%) Papillary and 29(16.6%) Chromophobe were selected. The association between expression of this marker and tumor characteristics was then analyzed.Results: Nanog was observed as cytoplasmic or nuclear expression but it was mainly localized to the cytoplasm of tumour cells. The mean cytoplasmic and nuclear expression of Nanog is highly significant different in RCC subtypes (P<0.001).There was a signiï پcant difference in the cytoplasmic expression of Nanog in the ccRCC samples compared to the ChRCC and pRCC samples (P <0.001). A signiï پcant difference was observed in the nuclear expression of Nanog in the ccRCC samples compared to the ChRCC and pRCC samples (sequentially P <0.001 and P=0.003).There is a positive correlation between cytoplasmic and nuclear expression of Nanog and RCC subtypes (P<0.001 and P=0.011). A significant association was found between cytoplasmic expression of Nanog and tumor size (P=0.024) and also nuclear expression of Nanog and metastasis to renal sinus (P=0.057).No significant association was found between nuclear and cytoplasmic expression of Nanog and clinicopathologic parameters including regional lymph node & renal vein involvements, microvasulcar invasion (MVI) and metastasis to the Gerota’s fascia, adrenal gland, peripheral fat, and renal pelvis. Conclusion: These findings suggest that in combination evaluation of cytoplasmic and nuclear expression of Nanog can be considered as valuable diagnostic markers for diagnosis of renal cancer stem cells and RCC sub types differentiation.

Keywords:

Nanog , Cancer stem cells (CSCs) , Renal cell carcinoma (RCC) , Tissue microarray (TMA)