title: Expression of RUNX3 and β-catenin in the carcinogenesis of sporadic colorectal tubular adenoma.
abstract: The aim of this study is to investigate the possible roles of runt-related transcription factor 3 (RUNX3) and β-catenin in the carcinogenesis of sporadic colorectal tubular adenomas. The expression of the RUNX3 and β-catenin proteins was evaluated by immunohistochemistry in 23 normal colorectal mucosa (NCM), 81 sporadic colorectal tubular adenomas with different dysplasias (SCTA-D) (mild n=33, moderate n=23, and severe n=25 dysplasia), and 48 sporadic colorectal tubular adenomas with cancerous changes (SCTA-Ca). RUNX3 methylation was assessed by methylation-specific polymerase chain reaction (MSP), combined with laser capture microdissection (LCM), in 17 NCM, 41 SCTA-D (mild n=15, moderate n=12, and severe n=14 dysplasia), and 17 SCTA-Ca tissues. Compared to NCM (82.6 %), RUNX3 in SCTA-D (54.3 %) and SCTA-Ca (27.1 %) was significantly downregulated (P<0.05). In NCM, SCTA-D, and SCTA-Ca, the incidence of positive expression for β-catenin was 13.0, 60.5, and 79.2 %, respectively. A statistically significant difference was observed (P<0.05). RUNX3 levels were markedly higher in adenoma with mild dysplasia (75.8 %) and moderate dysplasia (60.9 %) than in adenoma with severe dysplasia (20.0 %) (both with P<0.05). Likewise, the expression of β-catenin in severe dysplasia adenoma was 84.0 %, which was significantly higher than that in mild dysplasia adenoma (39.4 %). An inverse correlation was found between the protein expression of RUNX3 and β-catenin in SCTA-D and SCTA-Ca (P<0.05). MSP results showed that RUNX3 methylation in NCM, SCTA-D, and SCTA-Ca was 5.9, 17.1, and 41.2 %, respectively, with a statistically significant difference between NCM and SCTA-Ca (P<0.05). However, no significant difference of RUNX3 methylation was observed among different dysplasia groups. RUNX3 and β-catenin play important roles in the carcinogenesis of sporadic colorectal tubular adenomas. In addition, hypermethylation of RUNX3 can downregulate its expression.
authors.affiliation: Department of Pathology, Second Hospital of Hebei Medical University, No 215, West Heping Rd, 050000, Shijiazhuang, Hebei, People's Republic of China.
authors.forename: Linna
authors.initials: L
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Cui
authors.forename: Airong
authors.initials: A
authors.lastname: Cui
authors.forename: Wenxin
authors.initials: W
authors.lastname: Wu
mesh_terms: D000236:Adenoma / Q000737:chemistry / Q000209:etiology* / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000209:etiology* / Q000473:pathology; D050677:Core Binding Factor Alpha 3 Subunit / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D019175:DNA Methylation; D006801:Humans; D011401:Promoter Regions, Genetic; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000032:analysis / Q000502:physiology*
chemical_list: C495270:CTNNB1 protein, human; D050677:Core Binding Factor Alpha 3 Subunit; C493729:Runx3 protein, human; D051176:beta Catenin