title: 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. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.|GRECC, Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee.
authors.forename: Timothy
authors.initials: T
authors.lastname: Su
authors.affiliation: Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: M Kay
authors.initials: MK
authors.lastname: Washington
authors.affiliation: Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Reid M
authors.initials: RM
authors.lastname: Ness
authors.affiliation: Division of Gastroenterology/Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Rex
authors.affiliation: Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Walter E
authors.initials: WE
authors.lastname: Smalley
authors.affiliation: Department of Pathology & Laboratory Medicine, Indiana Pathology Institute, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Ulbright
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.|GRECC, Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee.
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.|GRECC, Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.|GRECC, Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee.
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Shrubsole
mesh_terms: D000236:Adenoma / Q000453:epidemiology / Q000473:pathology*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D003106:Colon / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007196:Indiana / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000473:pathology*; D012007:Rectum / Q000473:pathology*; D013714:Tennessee / Q000453:epidemiology
chemical_list: D014408:Biomarkers, Tumor
keywords: biomarkers; colorectal adenoma; distal; immunohistochemistry; proximal; β-catenin