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.

Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) in differential diagnosis between low malignant potential (LMP) and malignant ovarian tumours.

BACKGROUND: Matrix metalloproteinase-2 (MMP-2) (gelatinase A) and MMP-9 (gelatinase B) have the ability to degrade several extracellular matrix components. This study aimed to evaluate whether matrix metalloproteinases (MMP-2, MMP-9, MMP-2-TIMP-2 complex) or their tissue inhibitors (TIMP-1, TIMP-2) could be used as preoperative serum markers in differentiating between low malignant potential (LMP) and malignant ovarian tumours. PATIENTS AND METHODS: The study population consisted of 61 patients with ovarian neoplasms (28 benign, 11 LMP and 22 malignant). MMP-2, MMP-9, MMP-2-TIMP-2 complex, TIMP-1 and TIMP-2 were analysed from serum samples using enzyme-linked immunoassay (ELISA). RESULTS: Serum TIMP-1 values significantly increased from benign (median 250 microg/l, range 137-616 microg/l) to LMP (median 357 microg/l, range 63-587 microg/l) and further to malignant (median 443 microg/l, range 199-983 microg/l) ovarian neoplasms (p<0.001). There was a significant difference in the ratios of TIMP-1 to MMP-2 and TIMP-1 to MMP-2-TIMP-2 complex between the patients with benign vs. malignant and an LMP vs. malignant tumour. CONCLUSION: The value of circulating TIMP-1 and the ratios of TIMP-1 to MMP-2 and TIMP-1 to MMP-2-TIMP-2 complex may be valuable for differentiating between LMP and malignant ovarian tumours.