Correlation of Pathologic Features With CpG Island Methylator Phenotype (CIMP) by Quantitative DNA Methylation Analysis in Colorectal Carcinomaстатья из журнала
Аннотация: 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 ≥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≤0.05). Compared with MSI-L/non-CIMP, MSI-L/CIMP was associated with tumors that had <50% signet ring cell component, marked tumor infiltrating lymphocytes, and poor differentiation (all P<0.05). In conclusion, several pathologic features that have previously been shown to be associated with MSI are also significantly associated with CIMP. Both MSI and CIMP appear to play a role in the pathogenesis of specific morphologic patterns of colorectal carcinoma.
Год издания: 2006
Авторы: Shuji Ogino, Robert D. Odze, Takako Kawasaki, Mohan Brahmandam, Gregory J. Kirkner, Peter W. Laird, Massimo Loda, Charles S. Fuchs
Издательство: Lippincott Williams & Wilkins
Источник: The American Journal of Surgical Pathology
Ключевые слова: Epigenetics and DNA Methylation, Genetic factors in colorectal cancer, Cancer-related gene regulation
Другие ссылки: The American Journal of Surgical Pathology (HTML)
PubMed (HTML)
PubMed (HTML)
Открытый доступ: closed
Страницы: 1175–1183