Title | Correlation of pathologic features with CpG island methylator phenotype (CIMP) by quantitative DNA methylation analysis in colorectal carcinoma. |
Publication Type | Journal Article |
Year of Publication | 2006 |
Authors | Ogino S, Odze RD, Kawasaki T, Brahmandam M, Kirkner GJ, Laird PW, Loda M, Fuchs CS |
Journal | Am J Surg Pathol |
Volume | 30 |
Issue | 9 |
Pagination | 1175-83 |
Date Published | 2006 Sep |
ISSN | 0147-5185 |
Keywords | Cell Differentiation, Cohort Studies, Colorectal Neoplasms, CpG Islands, DNA Methylation, Humans, Lymphocytes, Microsatellite Repeats, Necrosis, Phenotype, Polymerase Chain Reaction, Promoter Regions, Genetic, Prospective Studies |
Abstract | Extensive gene promoter methylation in colorectal carcinoma has been termed the CpG island methylator phenotype (CIMP). Previous studies on CIMP used primarily methylation-specific polymerase chain reaction (PCR), which, unfortunately, may detect low levels of methylation that has little or no biological significance. Utilizing quantitative real-time PCR (MethyLight), we measured DNA methylation in a panel of 5 CIMP-specific gene promoters (CACNA1G, CDKN2A (p16), CRABP1, MLH1, and NEUROG1) in 459 colorectal carcinomas obtained from 2 large prospective cohort studies. CIMP was defined as tumors that showed methylation in >or=4/5 promoters. CIMP was significantly associated with the presence of mucinous or signet ring cell morphology, marked Crohn's-like lymphoid reaction, tumor infiltrating lymphocytes, marked peritumoral lymphocytic reaction, tumor necrosis, tumor cell sheeting, and poor differentiation. All these features have previously been associated with microsatellite instability (MSI). Therefore, we divided the 459 colorectal carcinomas into 6 subtypes, namely, MSI-high (MSI-H)/CIMP, MSI-H/non-CIMP, MSI-low (MSI-L)/CIMP, MSI-L/non-CIMP, microsatellite stable/CIMP, and micro satellite sstable/non-CIMP. Compared with MSI-H/non-CIMP, MSI-H/CIMP was associated with marked tumor infiltrating lymphocytes, tumor necrosis, sheeting, and poor differentiation (all P |
DOI | 10.1097/01.pas.0000213266.84725.d0 |
Alternate Journal | Am J Surg Pathol |
PubMed ID | 16931963 |
Grant List | R01 CA075090 / CA / NCI NIH HHS / United States P01 CA55075-13 / CA / NCI NIH HHS / United States P01 CA87969-03 / CA / NCI NIH HHS / United States |
Related Faculty:
Massimo Loda, M.D.