Metachronous cancer development in patients with sporadic colorectal adenomas—multivariate risk model with independent and combined value of hTERT and survivin

Background and aims Accurate, long-term risk predictors for colorectal cancer development in patients with sporadic adenomas are lacking. We sought to validate biomarkers predictive of metachronous colorectal cancer (mCRC) in patients with sporadic colorectal adenomas, using 374 consecutive patients from a large defined population. Materials and methods Risk evaluation was performed for patient and adenoma risk factors (morphometric longest nuclear axis and immunohistochemical markers survivin , human telomerase reverse transcriptase ( hTERT ), β-catenin , p16INK4a , p21CIP1 , and cyclin D1 ). Diagnostic accuracy was assessed by receiver-operating characteristics curve analysis, and uni- and multivariate survival analysis was performed. Results/findings Of the 374 patients, 26 (7%) developed mCRC with a median of 5.6 years (range 2–19) from index adenoma. Independent risk factors included age greater than or equal to 60 years, proximal location, multiplicity (greater than or equal to three adenomas), and high-grade neoplasia, with high-grade intraepithelial neoplasia and proximal location as the strongest on multivariate analysis (hazard ratio [HR] of 4.1 and 5.2, respectively; both p