Immunohistochemical expression of CD44, matrix metalloproteinase2 and matrix metalloproteinase9 in renal cell carcinomas.

PURPOSE: The aim of our study was to investigate the clinicopathologic values of the expression of CD44, matrix metalloproteinase (MMP)2, and MMP9 in renal cell carcinoma (RCC).

PATIENTS AND METHODS: A total of 107 clear cell RCCs (ccRCCs) and 32 nonclear cell RCCs (non-ccRCCs) were examined for CD44, MMP2, and MMP9 expression by immunohistochemistry. The membrane and cytoplasmic expression levels of the 3 proteins were scored by semiquantitative methods, and the correlations of the 3 proteins with clinicopathological parameters were verified.

RESULTS: The expression levels of CD44, MMP2, and MMP9 were positively correlated with nuclear grade (grade 1-2 vs. grade 3-4) (P = 0.003, P < 0.001 and P < 0.001, respectively) in the ccRCCs, while in the non-ccRCCs, only CD44 expression was correlated with higher nuclear grade (grade 1-3 vs. grade 4) (P = 0.001). Furthermore, CD44 expression in ccRCCs and non-ccRCCs was correlated with shorter overall survival in the univariate analyses (P < 0.001 and P = 0.015, respectively). In the multivariate analysis, which accounted for age, sex, nuclear grade, and pathologic stage, CD44 expression was an independent predictor of shorter overall survival only in ccRCCs. Correlations among the 3 proteins were all positive in ccRCCs, but in non-ccRCCs, only MMP2 and MMP9 were positively correlated.

CONCLUSION: CD44 expression may play an important role in the progression of both ccRCC and non-ccRCC. CD44 expression in ccRCC may be associated with elevated MMP2 and MMP9 expression levels, which is in contrast to non-ccRCC. The different correlations between CD44, MMP2, and MMP9 in ccRCC and non-ccRCC can be useful in understanding the mechanisms of carcinogenesis and stratifying patients for therapeutic purposes.