Does the Immunohistochemical Expression of CD44, MMP-2, and MMP-9 in Association with the Histopathological Subtype of Renal Cell Carcinoma Affect the Survival of Patients with Renal Cancer?

SIMPLE SUMMARY: The clinical outcomes of renal cell carcinoma (RCC) differ widely, indicating the need for accurate prognostic parameters. Because cancer stem cells and matrix metalloproteinases play a key role in carcinogenesis, CD44, MMP-2, and MMP-9 may be the potential prognosticators for RCC. The aim of our study was to analyse whether the immunohistochemical expression of these molecules in association with the histopathological RCC subtype affects patients’ survival. Significant differences existed in the degree of MMP expression between clear-cell RCC and non-clear cell RCC cases, which suggests different tumorigenic mechanisms between these subtypes. On multivariate analysis, only the histopathological subtype of clear cell RCC and CD44 expression were independent risk factors for patient death. Thus, CD44 seems to be an independent factor of poor outcomes in patients with RCC regardless of its subtype. It may be useful in the search for new therapeutic methods and in predicting the prognosis of patients with RCC. ABSTRACT: CD44, MMP-2, and MMP-9 are new potential molecular prognostic markers in renal cell carcinoma (RCC). The aim of the study was to analyze whether the expression of CD44, MMP-2, and MMP-9 in association with the histopathological subtype of RCC affects the survival of patients with renal cancer. The study population included 243 clear cell RCC (ccRCC) and 59 non-ccRCC cases. A total of 302 tumors were examined for CD44, MMP2, and MMP9 expression by immunohistochemistry. The expression levels of the proteins were scored by semi-quantitative methods, and the correlation with overall patient survival was verified. We found no significant differences in CD44 expression levels between cc-RCC and non-ccRCC cases; however, significant differences existed in the degree of MMP-2 and MMP-9 expression between cc-RCC and non-ccRCC cases. There was significantly higher MMP expression in non-ccRCC than in ccRCC cases. Univariate Cox regression analysis showed that increased CD44 expression and histopathological subtype of ccRCC were predictors of shorter overall survival. Moreover, MMP-2 overexpression slightly reduced the risk of patient death, while MMP-9 expression did not show an association with patients’ survival. However, on multivariate analysis, only the histopathological subtypes of ccRCC and CD44 expression were independent risk factors for patient death.