Low-grade slightly elevated and polypoid colorectal adenomas display differential β-catenin-TCF/LEF activity, c-Myc, and cyclin D1 expression

AIM To comparatively investigate the cellular and molecular characteristics of low-grade slightly elevated adenomas and polypoid adenomas. METHODS Colorectal tumors were collected from 24 patients with slightly elevated adenomas and 23 patients with polypoid adenomas. Five commonly mutated genes (APC, BRAF, KRAS, NRAS, and PIK3CA) were selected for mutational analysis. Paraffin-embedded tumor sections were used to calculate the apoptotic index (AI) and Ki-67 labeling index (KLI). Two pure colorectal epithelial cell lines were created by pooling the slightly elevated and polypoid tumors. Western blots, luciferase assays for beta-catenin-T-cell factor protein/beta-cateninlymphoid enhancer factor (beta-catenin-TCF/LEF)-driven transcriptional activity, and caspase activity assays were conducted on the two cell lines. RESULTS Slightly elevated lesions showed a significantly lower APC mutational frequency and a significantly higher KRAS mutational frequency both < 0.05). Slightly elevated lesions showed a significantly lower AI (P < 0.05). beta-catenin and beta-catenin-TCF/LEF-driven transcriptional activity was significantly upregulated in slightly elevated lesions (both P < 0.05). In slightly elevated lesions, c-Myc was significantly downregulated, while cyclin D1 was significantly upregulated (both P < 0.05). beta-catenin-TCF/LEF-driven transcriptional activity was negatively correlated with c-Myc (rho = -0.78). Slightly elevated lesions displayed significant Bcl-2 and Bcl-xL upregulation (both P < 0.05) along with significant decreases in caspase-9 and caspase-3 activity (both P < 0.05). c-Myc was negatively correlated with Bcl-2 and Bcl-xL (rho = -0.74 and -0.78, respectively). CONCLUSION The lower apoptotic activity of low-grade slightly elevated adenomas can be partly attributed to upregulated beta-catenin pathway activity and downregulated c-Myc expression.