Matrix metalloproteinase-2 and matrix metalloproteinase-9 codistribute with transcription factors RUNX1/AML1 and ETV5/ERM at the invasive front of endometrial and ovarian carcinoma

Abstract

Several matrix metalloproteinases (MMPs) are implicated in the degradation of the epithelial basement membrane (BM), invasiveness, and malignancy of endometrial and ovarian carcinomas. We have recently proposed a cooperative role for RUNX1/AML1 and ETV5/ERM in myometrial infiltration during endometrioid endometrial invasiveness. In the present work, we have characterized the occurrence, levels of expression, and codistribution of gelatinases MMP-2 and -9, and the transcription factors RUNX1/AML1 and ETV5/ERM, together with collagen type IV and laminin chains of the epithelial BM in endometrioid endometrial (EEC) and ovarian endometrioid carcinoma (OEC). MMP-2 and -9 expression levels were up-regulated at the invasive front of both carcinomas, and they showed a relatively high degree of volume codistribution with RUNX1/AML1 and ETV5/ERM. EEC tissue microarrays showed similar significant expression and correlation for MMPs and the transcription factors. When the array samples were grouped according to the carcinoma stages, there was significant correlation in the expression levels for both MMP-2 and -9 with ETV5/ERM. Colocalization of MMP-2 and -9 with epithelial basement membrane component collagen type IV showed close spatial association for both MMPs and discontinuation of collagen type IV expression at the invasive front in both EEC and OEC. BM components laminin α1, α2, α3, α5, and γ2 chains, laminin α5 receptor basal cell adhesion molecule (BCAM), and laminin 332 were all detected both in EEC and OEC. Highest expression levels in EEC were for laminin α3 and in OEC for laminin α5 chain. Laminin γ2 chain and laminin 332 showed discontinuous immunoreactivity in the epithelial basement membrane suggestive of proteolytic degradation. These results indicate concurrent mechanisms in expression of MMP-2 and -9, RUNX1/AML1 and ETV5/ERM, and several of the basement membrane components, which are likely to associate with the invasive stage of EEC and OEC.