Evaluation of expression of putative CSC marker CD44 in Renal Cell Carcinoma: A study using tissue microarrays (TMA)

INTRODUCTION: According to the cancer stem cell hypothesis, CSCs are immortal tumor-initiating cells that can self-renew and have pluripotent capacity. In addition, CSCs are resistance to chemotherapy agents and may play a relevant role in initiation and progression of tumors. CD44 is a multifunctional trans membrane glycoprotein that has been identified as a CSC marker in majority of cancers.OBJECTIVE: The aim of current study is to evaluate the expression level of CSC marker, CD44 with tumor clinicopathological features in different subtypes of renal cell carcinoma.METHODS: One hundred and ninety-five consecutive patients treated surgically for renal cell carcinoma (RCC) between 2010 and 2015 were selected including 125(64.1%) Clear Cell Renal Cell Carcinoma (ccRCC), 40 (20.5%) Papillary and 30 (15.4%) Chromophobe. The tumors were examined for the expression of CD44 using immunohistochemistry (IHC) method on tissue microarrays (TMA). The association between expression of this marker and tumor characteristics was then analyzed by correlation, chi square, kruskal- wallis test and Mann-Whitney test.RESULTS: Univarate analysis demonstrated that CD44 expression was significantly (P < 0.001) higher in Papillary (88.25%) compared to ccRCC (43.16%) and Chromophobe (15.33%) samples. Increased expression of CD44 was significantly correlated with higher grade tumors (P < 0.001). High expression of CD44 was associated with increased of stage. (P = 0.010). In addition, a statistically significant correlation was found between expression of CD44 and invasion to pelvis (P= 0.001), vein (P= 0.009) and lymph node (P= 0.011). Whereas CD44 expression was not correlated with other clinicopathologic features including tumor size (P= 0.507), age (P= 0.486), and sex (P= 0.501) of patients.CONCLUSIONS: These findings suggest that CD44 can be considered as a valuable tool for the study of renal CSCs and provide a therapeutic target for treatment of the patients with renal cell carcinoma in combination with conventional therapy.