Rojiani Mumtaz V, Alidina Janeen, Esposito Nicole, Rojiani Amyn M
Department of Pathology and Cell Biology, University of South Florida, Tampa, FL, USA.
Int J Clin Exp Pathol. 2010 Oct 16;3(8):775-81.
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.
基质金属蛋白酶（MMP）可能通过与细胞外基质和血管生成的相互作用，参与肿瘤侵袭和转移潜能的增加。本研究调查了一系列转移性中枢神经系统（CNS）肺癌中MMP-2免疫表达与血管生成之间的关系。从莫菲特癌症中心的存档中识别出28例具有足够脑肿瘤界面的转移性癌病例。使用针对前体和活性形式的抗体（NeoMarkers）通过免疫组织化学测定MMP-2表达。同样，在平行切片上用抗CD34抗体（Biogenix）识别微血管。通过Image Pro Plus图像分析系统对肿瘤内和CNS/肿瘤界面处的血管生成情况进行形态计量评估。简要地说，对CD34阳性血管进行定量，并与肿瘤中MMP-2表达的有无相关联。在脑肿瘤界面区域和肿瘤内评估平均微血管面积（MMVA）和平均微血管数量（MMVN），并表示为相对于肿瘤的比率。16例（57.14%）转移性肿瘤对MMP-2呈强免疫反应性，而12例（42.86%）为阴性。与MMP-2阴性肿瘤相比，MMP-2阳性肿瘤在CNS/肿瘤界面处的MMVA和MMVN比率更高。因此，MMP-2表达似乎赋予增强的血管增殖，特别是在脑肿瘤界面处，这将支持在CNS内生长和侵袭能力增强的观点，可能由MMP2调节。MMP-2表达与血管生成之间的关系先前已有报道，其生物学和治疗意义仍然是研究的重点。
