Increased expression of beta-catenin, phosphorylated glycogen synthase kinase 3beta, cyclin D1, and c-myc in laterally spreading colorectal tumors.
Laterally spreading tumors (LSTs) are considered a special subtype of superficial colorectal tumor. This study was performed to characterize the clinicopathological features and examine activation of the Wnt/beta-catenin pathway in LSTs and protruded-type colorectal adenomas (PAs). Fifty LSTs and 54 PAs were collected, and their clinicopathological characteristics were compared. The expression of E-cadherin, beta-catenin, glycogen synthase kinase-3beta (GSK-3beta), phosphorylated GSK-3beta, (phospho-GSK-3beta), cyclin D1, and c-myc was investigated by immunohistochemical staining on serial sections. Patients with LSTs were significantly older than those bearing PAs (63.4 vs 47.4 years old; p<0.001). The mean size of LSTs was significantly larger than that of PAs (27.0 mm vs 14.6 mm; p<0.01). Forty-eight percent of LSTs were located in the proximal colon, which was significantly higher than that of PAs (18.5%; p<0.05). Expression of beta-catenin, phospho-GSK-3beta, cyclin D1, and c-myc was significantly increased in LSTs compared with PAs (p<0.05). However, E-cadherin and total GSK-3beta expression was not significantly different between the two groups. The level of beta-catenin expression correlated strongly with phospho-GSK-3beta, cyclin D1, and c-myc expression in LSTs but not in PAs. Our findings suggest that activation of the Wnt/beta-catenin pathway is more prevalent in LSTs than in PAs, suggesting that phosphorylation-dependent inactivation of GSK-3beta may be involved in LST carcinogenesis.
Wang
Jing
J
Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, China.
Wang
Xinying
X
Gong
Wei
W
Mi
Biantao
B
Liu
Side
S
Jiang
Bo
B
D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D019938:Cyclin D1 / Q000096:biosynthesis*; D038362:Glycogen Synthase Kinase 3 / Q000096:biosynthesis*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007150:Immunohistochemistry; D010766:Phosphorylation; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D051176:beta Catenin / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D051176:beta Catenin; D019938:Cyclin D1; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3