BACKGROUND & AIMS: The G1/S-phase controlling mechanism known as the RB pathway is commonly deregulated in human malignancies. Here, the abundance and localization of key components of the retinoblastoma (RB) pathway were determined in exophytic and flat colorectal adenomas. METHODS: Samples of normal colonic mucosa (n = 41) and flat (n = 45) and exophytic (n = 26) adenomas were examined immunohistochemically using antibodies to cyclins D1, D2, D3, cyclin-dependent kinase (CDK) 4, retinoblastoma protein (pRB), and the CDK inhibitors p16INK4a, p18INK4c, and p19INK4d. RESULTS: In normal colonic epithelium, cyclin D2 was undetectable; expression of cyclin D1, CDK4, and pRB correlated with proliferation; and p16, p18, p19, and cyclin D3 were most abundant in quiescent, differentiated cells. Adenomas showed elevated expression of cyclin D1 and pRB, frequent induction of cyclin D2, and absence of p16. No obvious abnormalities were found for p18, p19, or cyclin D3. Overexpressed cyclin D2 was more common among exophytic and pRB among flat adenomas, respectively. Elevated cyclin D1, D2, and CDK4 correlated with enhanced dysplasia. CONCLUSIONS: Aberrant expression of cyclins D1, D2, CDK4, p16, and pRB occur in significant subsets of exophytic and flat adenomas, particularly among cases with high-grade dysplasia. Such defects of the RB pathway may perturb cell-cycle control and thereby contribute an early step in colorectal tumorigenesis.
BACKGROUND & AIMS: The G1/S-phase controlling mechanism known as the RB pathway is commonly deregulated in humanmalignancies. Here, the abundance and localization of key components of the retinoblastoma (RB) pathway were determined in exophytic and flat colorectal adenomas. METHODS: Samples of normal colonic mucosa (n = 41) and flat (n = 45) and exophytic (n = 26) adenomas were examined immunohistochemically using antibodies to cyclins D1, D2, D3, cyclin-dependent kinase (CDK) 4, retinoblastoma protein (pRB), and the CDK inhibitors p16INK4a, p18INK4c, and p19INK4d. RESULTS: In normal colonic epithelium, cyclin D2 was undetectable; expression of cyclin D1, CDK4, and pRB correlated with proliferation; and p16, p18, p19, and cyclin D3 were most abundant in quiescent, differentiated cells. Adenomas showed elevated expression of cyclin D1 and pRB, frequent induction of cyclin D2, and absence of p16. No obvious abnormalities were found for p18, p19, or cyclin D3. Overexpressed cyclin D2 was more common among exophytic and pRB among flat adenomas, respectively. Elevated cyclin D1, D2, and CDK4 correlated with enhanced dysplasia. CONCLUSIONS: Aberrant expression of cyclins D1, D2, CDK4, p16, and pRB occur in significant subsets of exophytic and flat adenomas, particularly among cases with high-grade dysplasia. Such defects of the RB pathway may perturb cell-cycle control and thereby contribute an early step in colorectal tumorigenesis.
Authors: Hongyan Zhu; Urszula Dougherty; Victoria Robinson; Reba Mustafi; Joel Pekow; Sonia Kupfer; Yan Chun Li; John Hart; Kathleen Goss; Alessandro Fichera; Loren Joseph; Marc Bissonnette Journal: Mol Cancer Res Date: 2011-06-08 Impact factor: 5.852
Authors: Timothy Su; M Kay Washington; Reid M Ness; Douglas K Rex; Walter E Smalley; Thomas M Ulbright; Qiuyin Cai; Wei Zheng; Martha J Shrubsole Journal: Mol Carcinog Date: 2016-08-11 Impact factor: 4.784
Authors: Alicia M Cole; Kevin Myant; Karen R Reed; Rachel A Ridgway; Dimitris Athineos; Gijs R Van den Brink; Vanesa Muncan; Hans Clevers; Alan R Clarke; Peter Sicinski; Owen J Sansom Journal: Cancer Res Date: 2010-08-24 Impact factor: 12.701
Authors: Fleur Elise Marie Rijcken; Jan Jacob Koornstra; Tineke van der Sluis; Ek Wytske Boersma-van; Jan H Kleibeuker; Harry Hollema Journal: Dig Dis Sci Date: 2008-06 Impact factor: 3.199