title: Expression of MMP-2 correlates with increased angiogenesis in CNS metastasis of lung carcinoma.
abstract: Matrix metalloproteinases (MMP) have been implicated in increased invasive and metastatic potential of tumors, possibly via interactions with the extracellular matrix and angiogenesis. This study investigates the relationship between MMP-2 immunoexpression and angiogenesis in a series of lung carcinomas metastatic to the central nervous system (CNS). Twenty eight metastatic carcinoma cases with adequate brain-tumor interface were identified from the archives at the Moffitt Cancer Center. MMP-2 expression was determined by immunohistochemistry using an antibody directed against pro and active forms (NeoMarkers). Similarly, microvessels were identified on parallel sections with anti-CD34 antibody (Biogenix). Angiogenesis profiles within the tumor and at the CNS/tumor interface were morphometrically assessed by the Image Pro Plus image analysis system. Briefly, CD34 positive vessels were quantitated and correlated with presence or absence of MMP-2 expression in the tumor. Mean microvessel area (MMVA) and mean microvessel number (MMVN) were assessed within areas of brain-tumor interface and within the tumor and expressed as a ratio relative to the tumor. Sixteen (57.14%) metastatic tumors were strongly immunoreac-tive for MMP-2, while 12 (42.86%) were negative. MMP-2 positive tumors had a higher MMVA and MMVN ratio at the CNS/tumor interface in comparison to MMP-2 negative neoplasms. MMP-2 expression thus appears to confer enhanced vascular proliferation particularly at the brain-tumor interface which would support the contention of enhanced capability of growth and invasion within the CNS, possibly modulated by MMP2. The relationship between MMP-2 expression and angiogenesis has been previously reported and its biological and therapeutic implications remain the focus of investigations.
authors.affiliation: Department of Pathology and Cell Biology, University of South Florida, Tampa, FL, USA.
authors.forename: Mumtaz V
authors.initials: MV
authors.lastname: Rojiani
authors.forename: Janeen
authors.initials: J
authors.lastname: Alidina
authors.forename: Nicole
authors.initials: N
authors.lastname: Esposito
authors.forename: Amyn M
authors.initials: AM
authors.lastname: Rojiani
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply* / Q000556:secondary; D018952:Antigens, CD34 / Q000378:metabolism; D001932:Brain Neoplasms / Q000098:blood supply* / Q000556:secondary; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000098:blood supply* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000201:enzymology*
chemical_list: D018952:Antigens, CD34; D020778:Matrix Metalloproteinase 2