p16 gene methylation in colorectal cancers associated with Duke’s staging

Abstract

AIM To explore the association of methylation of the CpG island in the promotor of the P16 tumor suppressor gene with the clinicopath ological characteristics of the colorectal cancers.METHODS Methylation-specific PCR (MSP) was used to detect P16 methylation of 62 sporadic colorectal cancer specimens.RESULTS P16 methylation was detected in 42% of the tumors. Dukes' staging was associated with P16 methylation status. p16 methylation occurred more frequently in Dukes' C and D patients (75.9%) than in Dukes' A and B patients (12.1%).CONCLUSION P16 methylation plays a role in the carcinogenes is of a subset of colorectal cancer, and it might be linked to poor prognosis.

The blues of P(16)INK(4a): Aberrant promoter methylation and association with colorectal cancer in the Kashmir valley

“…We found a significant association of the p16INK4a methylation status with higher Dukes’ stage (C+D). These results are in concordance with those of other studies ( 20 , 21 , 23 ), which have reported the same observations of a higher methylation status of p16INK4a gene promoter with higher Dukes’ stage (C+D). Duke’s staging has been considered a most significant prognostic determinant in cancers ( 20 ).…”

“…In the present study, we observed hypermethylation of the p16INK4a gene promoter in 42.1% (48/114) of CRC cases, which is higher than reported by other major studies in the world ( 11 , 20 , 21 ). However, our observation is consistent with other studies ( 22 , 23 ) which have reported a similar frequency of p16INK4a hypermethylation in CRC tumours in the Japanese population.…”

Immunohistochemical analysis of thymidylate synthase, p16INK4a, cyclin‐dependent kinase 4 and cyclin D1 in colorectal cancers receiving preoperative chemotherapy: Significance of p16INK4a‐mediated cellular arrest as an indicator of chemosensitivity to 5‐fluorouracil

“…p16 INK4a , a product of the CDKN2/MTS1 gene located at the chromosomal region 9p21, is a negative regulator of G1/S‐phase transition that promotes cell‐cycle arrest via the Rb tumor suppressor pathway, and its expression increases along with the onset of cellular senescence 9–13 . In colorectal cancers, homozygous deletion and mutation of the CDKN2/MTS1 gene are reportedly very rare, 35–37 while methylation of the gene is detected in 18–53% of the cancer series 19,20 , 23,25 , 37 . Reportedly, inactivation of the CDKN2/MTS1 gene is generally associated with an aggressive phenotype and poor prognosis in a wide range of neoplasms, including colorectal cancers, 19,20 , 23,25 , 28 and is usually paralleled with loss or markedly reduced expression levels of p16 INK4a protein and mRNA 28,37 .…”

“…In colorectal cancers, homozygous deletion and mutation of the CDKN2/MTS1 gene are reportedly very rare, 35–37 while methylation of the gene is detected in 18–53% of the cancer series 19,20 , 23,25 , 37 . Reportedly, inactivation of the CDKN2/MTS1 gene is generally associated with an aggressive phenotype and poor prognosis in a wide range of neoplasms, including colorectal cancers, 19,20 , 23,25 , 28 and is usually paralleled with loss or markedly reduced expression levels of p16 INK4a protein and mRNA 28,37 . In the present immunohistochemical investigation, p16 INK4a expression was low in 68% of the resected tumors in the untreated control patients and in 71% of the preoperative biopsy specimens.…”

“…Alterations of the elements of p16 INK4a ‐mediated cellular arrest have frequently been reported in various types of cancers 14–28 . In particular, inactivation of the CDKN2/MTS1 gene leading to loss of p16 INK4a protein expression is associated with the biological aggressiveness of cancer cells and the poor prognosis of cancer patients 19,20 , 22–25,28 . As for the colorectal cancers, there have been several studies that assessed the relationship between the expression of p16 INK4a ‐associated cell cycle proteins and TS expression or patient outcome 16,18 , 21,23 , 27,29 .…”