Ovarian carcinoma cells in serous effusions show altered MMP-2 and TIMP-2 mRNA levels

The expression of matrix metalloproteinases (MMP) and their inhibitor TIMP- 2 in serous effusions from patients with ovarian carcinoma and its associat ion with clinico-pathological parameters were analysed. The findings in car cinoma cells in effusions were compared with corresponding primary and meta static lesions. Sixty-six effusions and 96 tissue sections were stained for MMP-1. MMP-2 and MMP-9 applying immunohistochemistry (IHC) and analysed fo r MMP-2, MMP-9 and TIMP-2 expression using mRNA in situ hybridisation (ISH) . MMP-2 and MMP-9 mRNA levels in 30 effusions were subsequently analysed us ing reverse transcription-polymerase chain reaction (RT-PCR). MMP and TIMP expression was detected in both carcinoma and mesothelial cells in effusion s. The levels were consistently higher in malignant cells, significantly so for MMP-1 (P = 0.016) and MMP-2 (P = 0.036) proteins. as well as for TIMP- 2 mRNA (P = 0.008). In tissue sections. MMP-1. MMP-2 and MMP-9 protein expr ession was mostly localised to tumour cells, while MMP-2. MMP-9 and TIMP-2 mRNA were predominantly detected in stromal cells. Adenocarcinoma cells in effusions showed a significant upregulation of MMP-2 expression compared wi th primary tumours, with a concomitant downregulation of TIMP-2. RT-PCR dem onstrated the presence of MMP-2 and MMP-9 in 28/30 and 0/30 specimens, resp ectively. MMP and TIMP are thus mainly synthesised by cancer cells in effus ions, while stromal cells have a similar role in solid tumours. MMP-1 and M MP-2 production predominates over that of MMP-9 in effusions. Increased MMP -2 and reduced TIMP-2 levels are seen in ovarian carcinoma cells in effusio ns, possibly marking the acquisition of a metastatic phenotype. (C) 2001 El sevier Science Ltd. All rights reserved.