Cell-cycle and Apoptosis Regulators (p16INK4A, p21CIP1, α-Catenin, Survivin, and hTERT) and Morphometry-Defined MPECs Predict Metachronous Cancer Development in Colorectal Adenoma Patients

摘要: Background and Aims: Although adenomas may be precursors to colorectal cancers (CRC), knowledge concerning the development of metachronous CRC is scarce. We assessed whether differential expression cell-cycle apoptosis-regulating proteins a monotonous population elongated cells (MPECs) in could predict CRC. Methods: Application immunohistochemistry on tissue microarrays consecutive, population-based adenomas. Influence classic features (e.g., intraepithelial neoplasia grade, histological type, size) was examined. Results: Of 171 patients with adenoma 86% (n = 147) were eligible for study; 10 (7%) developed Median time cancer 69 months (range, 25–256). follow-up equal non-cancer groups. Elevated cellcycle regulators p16INK4A, p21CIP1, cytoplasmic/nuclear α-catenin correlated increased risk (all P <0.0001), as did elevated anti-apoptosis protein survivin (P <0.0001) human telomerase reverse transcriptase (hTERT; <0.001). Survivin, hTERT, nuclear most predictive molecular markers (hazard ratios [HRs]: 6.3, 9.4, 5.8, respectively). In combined multivariate model, MPECs had best overall prognostic ability (HR 28.2, 95% CI: 3.6–223.0), together survivin, hTERT. Within containing MPECs, several further defined high-risk patients. Conclusions: Among adenomas, hTERT may, when validated, provide information superior conventional histology, relevance clinical management adenoma.