Expression of p53, bcl-2, E-cadherin, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinases-1 in paired primary tumors and brain metastasis

The objectives of this study were to: (a) characterize the immunohistochemi stry expression of p53, bcl-2, E-cadherin (EC), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1) in brain met astases; (b) compare immunohistochemical (IHC) expression of brain metastas es with their primary tumors; and (c) assess the prognostic value of expres sion of these markers. Tumors from 35 patients with brain metastasis mere s tudied for IHC expression of p53, bcl-2, EC, MMP-9, and TIMP-1, In 17 cases , primary tumors were also available for study. In brain metastases, p53 wa s positive in 91% of cases and intermediate in 9%, MMP-9 was positive in al l eases, TIMP-1 was intermediate in 6% and negative in 94% of cases, EC exp ression was positive in 86% of eases and intermediate in 14%, and bcl-2 was variable. All primary tumors were positive for p53 and MMP-9, 3% were inte rmediate for TIMP-1 and 97% were negative, 65% were positive for EC and 35% were intermediate, whereas bcl-2 expression was variable, Neither p53, bcl -2, TIMP-1, or EC staining correlated with overall survival or survival wit h brain metastases, No assessment of survival differences could be made for MMP-9 because of ifs overexpression in all tissues. This study found that MMP-9 and p53 were markedly overexpressed in primary tumors and matched bra in metastasis, TIMP-1 expression was negative in the majority of specimens, whereas EC expression was maintained in both primary tumors and brain meta stases and bcl-2 expression was variable. This study suggests that the func tional balance of MMP-9 and TIMP-1 Is shifted toward extracellular matrix d egradation in brain metastases and that deregulation of cell cycle control by p53 also exists in brain metastases, The high expression of EC may indic ate the importance of adherence at late stages of metastasis but requires f urther study.