Expression of MMP-2, MMP-9, and urokinase-type plasminogen activator in cervical intraepithelial neoplasia

Matrix metalloproteinase-2 (MMP-2), MMP-9, and urokinase-type plasminogen activator (uPA) are important factors for cancer invasion and metastasis, degrading the extracellular matrix. They are also associated with angiogenesis. Angiogenic phenotype is another feature of high-grade cervical intraepithelial neoplasia (CIN). However, their associations with the progression of low-grade CIN to high-grade CIN are unexplored. We investigated whether these proteolytic enzyme expressions correlate with the progression of CIN. A total of 39 paraffin-embedded specimens from 10 patients with CIN grade 1, nine with CIN grade 2, and 20 with CIN grade 3 were assessed immunohistochemically by specific antibodies against MMP-2, MMP-9, and uPA. MMP-9 expression was higher in CIN 3 lesions (47.4%) than in CIN 1 (22.2%) and CIN 2 (20.2%) lesions, although the difference failed to reach statistical significance. The expression level of uPA and MMP-2 was not associated with the grade of CIN lesions. Interestingly, we found a significant association between expressions of uPA and MMP-2 (P= 0.028). Our results suggest that MMP-9 might play a role in the progression of CIN.