Clinical significance of matrix metalloproteinase-2 in cancer of uterine cervix: A semiquantitative study of immunoreactivities using tissue array

Abstract

Objectives. To study the expression of matrix metalloproteinase-2 (MMP-2) in cancer of uterine cervix and correlate its expression with clinicopathological parameters, recurrence and survival of patients. Methods. Twenty cervical cancer and 20 normal tissues from the same patients were collected to detect MMP-2 mRNA expression. From them, 16 cancer and 16 normal tissues were collected and added with another 64 cancer tissues to construct a 96-tissue core microarray for immunohistochemical study. We evaluated the relationships among MMP-2 immunoreactivity using semiquantitative H scores, obtained by multiplying proportion score of stained cells and their mean digital density, and clinicopathological variables, recurrence and survival in cervical cancer patients. We used univariate and multivariate analyses of all parameters for recurrence and survival, further including time interval for evaluation. Results. MMP-2 mRNA expression was higher in most of cervical cancerous tissues than normal counterparts. H score of MMP-2 was significantly higher in cancerous tissue cores than normal counterparts (median H scores: 1.5 vs. 0.3, P < 0.001). MMP-2 expression was significantly associated with parametrium invasion ( P = 0.004) and lymph node metastasis ( P = 0.015), but not with cancer recurrence, recurrence-free and overall survival rates of these patients. However, poor tumor cell differentiation and positive parametrium invasion significantly increased the recurrence and poor cell differentiation increased the risk of death. Conclusions. MMP-2 is highly expressed in cervical cancer tissues at mRNA and protein levels and associated with lymph node metastasis and parametrium invasion but not predictive of recurrence and survival in cervical cancer patients.