Liver expression of matrix metalloproteases and their inhibitors in hepatocellular carcinoma

• Published in: Digestive and liver disease 2009-10, Vol.41 (10), p.740-748
• Main Authors: Altadill, A, Rodríguez, M, González, L.O, Junquera, S, Corte, M.D, González-Dieguez, M.L, Linares, A, Barbón, E, Fresno-Forcelledo, M, Rodrigo, L, Vizoso, F.J
• Format: Article
• Language: English
• Subjects: Aged; Carcinoma, Hepatocellular - diagnosis; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - mortality; Female; Follow-Up Studies; Gastroenterology and Hepatology; Hepatocellular carcinoma (HCC); Humans; Liver - cytology; Liver - metabolism; Liver Neoplasms - diagnosis; Liver Neoplasms - metabolism; Liver Neoplasms - mortality; Male; Matrix metalloproteases (MMPs); Matrix Metalloproteinase 1 - metabolism; Matrix Metalloproteinase 13 - metabolism; Middle Aged; Prognosis; Stromal Cells - metabolism; Survival Analysis; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Tissue Inhibitor of Metalloproteinase-2 - metabolism; Tissue inhibitors of metalloproteinases (TIMPs)
• ISSN: 1590-8658; 1878-3562
• DOI: 10.1016/j.dld.2009.01.016

Abstract Background Several studies have suggested the significance of some metalloproteases in the malignant behaviour of hepatocellular carcinoma. Aims To evaluate the liver expression of MMPs and their tissular inhibitors in patients with HCC. Methods An immunohistochemical study using tissue microarrays on samples obtained from 30 HCC patients, with antibodies against MMPs (1, 2, 7, 9, 11, 13 and 14) and TIMPs (1, 2 and 3) was performed. Results were correlated with various clinico-pathological findings and with overall survival. Results MMP-1 is mainly expressed by stromal cells, and MMP-13, TIMP-1 and TIMP-2 by inflammatory cells. A positive correlation between MMP-1 expression and larger size tumours ( p < 0.01) was found. Increased TIMP-2 expression was associated with higher preoperative serum levels of α-fetoprotein ( p < 0.01). Unsupervised hierarchical clustering for total score values designated two groups, one of them characterised by high MMPs and TIMPs expressions, including 21 cases (70%) for tumour cell clustering, 5 cases for fibroblasts (16.6%) and 6 cases for inflammatory cells (20%). All patients showing elevated MMPs and TIMPs expression in stromal cells presented a poor prognosis ( p < 0.05). Conclusions High liver MMPs and TIMPs expressions in peritumour stromal cells are related to a poorer prognosis in HCC.