Abstract 2853: Apoptosis and proliferation in micropapillary structures of colorectal polyps and carcinomas

Abstract

Abstract Background: Micropapillary structures (MIP) can be defined as focal piles of epithelial cells in columnar epithelium. MIP's are found in many cancers, but they are characteristic for serrated colorectal carcinomas. Suprabasal cells of MIP show no contact with extracellular matrix (unpublished). Objective: To evaluate whether MIP cells in colorectal polyps and cancers would show evidence for anoikis inhibition we assessed proliferation and apoptosis indexes (PI and AI, respectively) in MIP and non-MIP epithelium. Materials and methods: We stained human colorectal lesions: non-serrated adenomas (n = 15), serrated polyps (n = 29), conventional adenocarcinomas (n = 32), and serrated adenocarcinomas (n = 30) with antibodies to Ki67 and M30. To obtain PI and AI two independent observers counted proportions of positive cells separately in the cells of MIP and in non-MIP epithelium. Results: In carcinomas, AI was lower in the cells of MIP (M30; median 0, range 0-40) than in the non-MIP cells (median 2, range 0-40; p<0.001, Wilcoxon). Similarly, PI was lower in the MIP cells (Ki67; MIP: median 17, range 0-93; non-MIP: median 30, range 1-93; p<0.001). Similar patterns were evident in subsets of serrated lesions, in both carcinomas (p<0.001) and polyps (p<0.001), and in non-serrated carcinomas (p<0.004). Apoptosis/proliferation (AI/PI) ratio was lower in the MIP cells than in the non-MIP epithelium in both cancers and their precursor lesions (P<0.01). Conclusion: Apoptosis rate was lower in MIP's than in other tumor epithelium indicating ability of these cells to survive without matrix contact, i.e. Anoikis is inhibited in them. Lower PI could suggest that cells in the MIP are in some kind of quiescent stage. However, significantly lower AI/PI ratio in the MIP infers that these structures may form a fast growing subpopulation of tumor cells. Further studies are in progress to dissect mechanism of formation of MIP and matrix independent survival of tumor cells in them. Citation Format: Madhura Patankar, Sara Vayrynen, Anne Tuomisto, Markus Makinen, Tuomo Karttunen. Apoptosis and proliferation in micropapillary structures of colorectal polyps and carcinomas. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2853.