Immunohistochemical Expression of CD44, MMP-2, MMP-9, and Ki-67 as the Prognostic Markers in Non-Clear Cell Renal Cell Carcinomas-A Prospective Cohort Study.

Abstract

CD44 is the most frequently reported marker of the cancer stem cells in renal cell carcinoma (RCC). Matrix metalloproteinases MMP-2 and MMP-9 are key regulators of tumor invasion and metastasis. The aim of this study was to investigate the clinicopathologic and prognostic values of the immunohistochemical expression of CD44, MMP2, MMP9, and Ki-67 in papillary and chromophobe RCCs. In the case of papillary RCC, MMP-2 expression was positively correlated with patient age (p < 0.05), while CD44 expression was positively correlated with tumor stage (τ = 0.26, p < 0.05). Moreover, CD44 expression positively correlated with MMP-9 (τ = 0.39, p < 0.05). In the case of chromophobe RCC, only Ki-67 expression was negatively correlated with tumor stage (τ = −0.44, p < 0.05). During follow-up, a death was documented in 6 patients with papillary RCC. In these patients, CD44 expression was not a significant factor affecting the overall survival of patients (p > 0.05), whereas there was a positive correlation between increased MMP-9 expression and shorter overall survival (p < 0.05). Taken together, carcinogenesis in papillary RCC is probably dependent on both cancer stem cells and metalloproteinases activity. Expression of CD44 and MMP-9 can significantly improve the prediction of papillary RCC prognosis in the future.