Abstract LB-341: Immunohistochemical features differentiating newly formed from pre-existing vasculatures .

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Objectives of the study: A great number of in vitro and in vivo studies have suggested that a number of pathways and factors can stimulate angiogenesis and lymphangiogenesis, which facilitate tumor progression and metastasis. The morphological and immunohistochemical profile of newly formed vasculatures, however, has not been elucidated, making it difficult, if not impossible, to differentiate them from the pre-existing ones, and to identify their unique molecular profiles for therapeutic interventions. Methodology: Consecutive tissue sections from 100 age- and type-matched colorectal cancer (CRC) patients with and without positive lymph nodes were subjected to double or triple immunohistichemistry with a panel of stem cell and vasculature-related markers, including cytokeratin (CK) 19, CD133, D2-40, CD31, and CD34. Expression of these markers in morphologically distinct large and small vasculatures with and without disseminated tumor cells was compared. Results: Our study revealed that the endothelial cells of all morphologically distinct large and small vasculatures without disseminated tumor cells within their lumen only expressed either lymphatic duct or blood vessel phenotypic markers. Our study also revealed that a subset of lymph node-positive cases harbored some isolated normal epithelial structures with distinct CK-19 immunostaining within an otherwise CK-19-negative background. These epithelial structures were exclusively located within or adjacent to lymphoid follicles and were often surrounded by tube-like structures that express high levels of lymphatic endothelial marker D2-40. These tube-like structures were more frequently seen at the junctions between pre-invasive and invasive CRC with the following features: (1). they consist of a single layer of endothelial cells that express high levels of both lymphatic duct and blood vessel phenotypic markers, (2). their endothelial walls are often incomplete with disseminated cells physically connected with the adjacent stromal cells or tumor cells within the stroma, and (3). disseminated tumor cells within their lumen express high levels of CK-19. Conclusions: Based on these and other findings, we propose that these tube-like structures represent newly formed vasculatures, which are derived by the convergence of aberrant lymphocyte infiltration and tumor stem cells. Because of their close physical proximity, tumor stem cells within the epithelial and stromal components contribute equally and coordinately to the morphogenesis of new vasculatures that constitutes the basis for the unique morphologic and immunohistochemical features of newly formed vasculatures. Citation Format: Bin Jiang, Myron Arlen, Hongyan Yuan, yan-gao man. Immunohistochemical features differentiating newly formed from pre-existing vasculatures . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-341. doi:10.1158/1538-7445.AM2013-LB-341