Comparison of biomarker expression between proximal and distal colorectal adenomas: The Tennessee–Indiana Adenoma Recurrence Study

Abstract

It is unclear if proximal and distal traditional adenomas present with differences in molecular events which contribute to cancer heterogeneity by tumor anatomical subsite. Participants from a colonoscopy-based study (n=380) were divided into subgroups based on the location of their most advanced adenoma: proximal, distal, or “equivalent both sides”. Eight biomarkers in the most advanced adenomas were evaluated by immunohistochemistry (Ki-67, COX-2, TGFβRII, EGFR, β-catenin, cyclin D1, c-Myc) or TUNEL (apoptosis). After an adjustment for pathological features, there were no significant differences between proximal and distal adenomas for any biomarker. Conversely, expression levels did vary by other features, such as their size, villous component, and synchronousness. Large adenomas had higher expression levels of Ki-67(P<0.001), TGFβRII (P<0.0001), c-Myc (P<0.001), and cyclin D1 (P<0.001) in comparison to small adenomas, and tubulovillous/villous adenomas also were more likely to have similar higher expression levels in comparison to tubular adenomas. Adenoma location is not a major determinant of the expression of these biomarkers outside of other pathological features. This study suggests similarly important roles of Wnt/β-catenin and TGF-β pathways in carcinogenesis in both the proximal and distal colorectum.

Are Stem Cell Marker Expression and Cd133 Analysis Relevant to Differentiate Colorectal Cancer?

“…Another immunohistochemical study was performed in 380 adenomas for differences in molecular Ki-67, COX-2, TGFβRI, EGFR, β-catenin, cyclin D1, c-MYC and TUNEL (apoptosis) mutations of proximal and distal adenomas, which may contribute for cancer heterogeneity between the two topographies. The authors concluded that the adenoma location is not one of the main determiners of expression of the analyzed biomarkers outside of other pathological features 21 . Another research evaluated the expression of 29 markers of 50 patients pairing their neoplastic tissue (from adenoma to hepatic metastasis) with a normal mucosa sample.…”