Inactivation of p16INK4a by CpG hypermethylation is not a frequent event in colorectal cancer

Norrie, Mark W. A., Hawkins, Nicholas J., Todd, Alison V., Meagher, Alan P., O'Connor, Terence W. and Ward, Robyn L. (2003) Inactivation of p16INK4a by CpG hypermethylation is not a frequent event in colorectal cancer. Journal of Surgical Oncology, 84 3: 143-150. doi:10.1002/jso.10310


Author Norrie, Mark W. A.
Hawkins, Nicholas J.
Todd, Alison V.
Meagher, Alan P.
O'Connor, Terence W.
Ward, Robyn L.
Title Inactivation of p16INK4a by CpG hypermethylation is not a frequent event in colorectal cancer
Formatted title
Inactivation of p16INK4a by CpG hypermethylation is not a frequent event in colorectal cancer
Journal name Journal of Surgical Oncology   Check publisher's open access policy
ISSN 0022-4790
1096-9098
Publication date 2003-11
Sub-type Article (original research)
DOI 10.1002/jso.10310
Open Access Status Not yet assessed
Volume 84
Issue 3
Start page 143
End page 150
Total pages 8
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Language eng
Formatted abstract
Backround and Objectives: Gene promoter hypermethylation is common in colorectal cancer and is associated with transcriptional silencing. However, the clinicopathological significance of p16INK4a gene silencing with hypermethylation is unknown. Therefore, the aim of this study was to analyze loss of p 16 expression and its relationship to hypermethylation in sporadic colorectal cancer.

Methods: Tissue from 426 colorectal cancers underwent histological analysis. Immunohistochemistry was performed for p16 expression. Fresh tumor DNA was analyzed for microsatellite instability (MSI) and the presence of K-ras mutations. In addition, DNA was bisulphite-modified and analyzed for p16INK4a promoter methylation by methylation-specific PCR.

Results: There were 25% of tumors with p16INK4a promoter hypermethylation. These tumors were associated with older patients, right-sidedness, MSI and were poorly differentiated, mucinous, and had intraepithelial and peritumoral lymphocytes and a Crohn's-type lymphocytic reaction (P < 0.05). However, only right-sidedness was significant on multivariate analysis (P < 0.001). Only 8.1% of tumors did not express p16, and this was associated with hypermethylation (P < 0.05).

Conclusion: p16INK4a promoter methylation, although common in colorectal cancer, does not result in a clinicopathologically distinct subgroup of tumors and infrequently results in transcriptional silencing. This suggests that P16INK4a gene inactivation does not have an important role in the pathogenesis of sporadic colorectal cancer.
Keyword Colorectal cancer
Immunohistochemistry
Methylation
Methylation-specific PCR
Microsatellite instability
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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