Prognostic and clinicopathological significance of CD44, MMP-2, and MMP-9 expression in clear cell renal cell carcinoma

Introduction: CD44 is a well-known marker for cancer stem cells. Matrix metalloproteinases MMP-2 and MMP-9 are essential for tumor growth, invasion, and metastasis. This study aimed to analyze clinicopathologic and prognostic values of CD44, MMP-2, and MMP-9 expression in clear cell renal cell carcinoma (ccRCC) patients. Material and methods: A total of 243 patients with a diagnosis of ccRCC were included in the study. All tumors were examined for CD44, MMP-2, and MMP-9 expression by immunohistochemistry. Membranous and cytoplasmic expression levels were scored by semiquantitative methods, and the correlation between clinicopathological parameters and patient outcome was investigated. Results: A positive correlation was attained between CD44 and MMP-2 and between CD44 and MMP-9 expression levels. CD44 was positively correlated with: grade, pathologic stage, tumor size, percentage of tumor necrosis and sarcomatoid transformation, presence of angioinvasion, and renal sinus fat invasion. Univariate analysis showed that patients with increased (moderate and high) CD44 expression had remarkably shorter overall survival than patients with lower CD44 expression. In turn, MMP-9 and MMP-2 were not positively correlated either with the clinicopathological parameters or with patients’ survival. Conclusions: CD44 mainly contributes to the aggressiveness of ccRCC and determines the decisive role of cancer stem cells in the mechanisms of ccRCC carcinogenesis. CD44 seems to be an independent factor of poor outcome, and therefore the authors consider it a valuable prognostic marker in patients with ccRCC. However, MMP-2 and MMP-9 might play roles during extracellular matrix invasion in certain aspects of ccRCC progression but do not affect long-term adverse events.