Increased matrix metalloproteinases 2 and 9 and tissue inhibitor of matrix metalloproteinase 2 expression is associated with progression from vulvar intraepithelial neoplasia to invasive carcinoma

Objective. The expression of matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9) and tissue inhibitors of matrix metalloproteinases 1 (TIMP-1) and 2 (TIMP-2) in vulvar intraepithelial neoplasia (VIN I-III) and in vulvar invasive carcinoma were evaluated. Design. A retrospective study. Setting. Oulu University Hospital, Finland. Sample. The study population consisted of 68 patients with vulvar neoplasia (13 VIN I, 5 VIN II, 6 VIN III and 44 squamous cell carcinomas). Methods. Paraffin-embedded tissue samples were examined by immunohistochemistry. Main outcome measures. MMP-2, MMP-9, TIMP-1 and TIMP-2 expression in VIN compared to vulvar carcinoma. Results. In VIN I-III MMP-2 expression was positive in 13%, MMP-9 in 13%, TIMP-1 in 50% and TIMP-2 in 17% of patients. The positive expressions in patients with vulvar carcinoma were 52% for MMP-2, 36% for MMP-9, 41% for TIMP-1 and 78% for TIMP-2. Conclusions. We conclude that over-expression of MMP-2, MMP-9 and TIMP-2 may be associated with the progression from VIN to invasive vulvar squamous cell carcinoma.