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Journal of Cancer Research and Clinical Oncology

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01.02.2010 | Original Paper

Aberrant p16^INK4a methylation is a frequent event in colorectal cancers: prognostic value and relation to mRNA expression and immunoreactivity

verfasst von: Hiroyuki Mitomi, Naoshi Fukui, Nobuho Tanaka, Hideki Kanazawa, Tsuyoshi Saito, Takashi Matsuoka, Takashi Yao

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 2/2010

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Abstract

Purpose

Aberrant p16^INK4a promoter methylation is common in colorectal cancer (CRC), but its clinicopathological significance remains controversial. The present study was therefore conducted to analyze p16^INK4a methylation and its relationship to clinicopathological features, mRNA levels and immunoreactivity in a series of lesions.

Methods

p16^INK4a methylation was assessed for normal mucosa (n = 30) and CRC samples (n = 212) by methylation-specific real-time quantitative PCR, and p16^INK4a expression by immunostaining in formalin-fixed paraffin-embedded specimens. In addition, fresh DNA (n = 61) was analyzed for relationships to p16^INK4a mRNA by reverse-transcription PCR.

Results

The p16^INK4a methylation index of normal mucosa samples ranged from 0 to 2% (mean, 0.23%; median, 0.02%), while the values for tumor samples varied widely from 0 to 100% (mean, 25.7%; median, 7.1%), the difference being statistically significant (P < 0.001). Of 151 paraffin-embedded CRC tissue samples, 51 (34%), 54 (36%), and 46 (30%) were classified as low, intermediate, and high for aberrant methylation of p16^INK4a. High p16^INK4a methylation was significantly associated with large tumor size (P = 0.025). Patients with higher methylation further showed more frequent recurrence as compared with the low-methylation group, and shortened cancer-related survival (Hazard ratio [HR], 3.379; P < 0.001) and recurrence-free survival (HR, 3.962; P < 0.001 on multivariate analysis). A significant inverse relationship was apparent between the p16^INK4a methylation and immunoreactivity (P = 0.017). A similar tendency was also observed for the methylation status and the mRNA level (P = 0.195).

Conclusions

We conclude that p16^INK4a methylation results in transcriptional silencing and defines a group of CRCs with a poor prognosis.

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Titel: Aberrant p16INK4a methylation is a frequent event in colorectal cancers: prognostic value and relation to mRNA expression and immunoreactivity
verfasst von: Hiroyuki Mitomi
Naoshi Fukui
Nobuho Tanaka
Hideki Kanazawa
Tsuyoshi Saito
Takashi Matsuoka
Takashi Yao
Publikationsdatum: 01.02.2010
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 2/2010
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-009-0688-z

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Aberrant p16^INK4a methylation is a frequent event in colorectal cancers: prognostic value and relation to mRNA expression and immunoreactivity

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Purpose

Methods

Results

Conclusions

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Springer Medizin

Abstract

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Conclusions

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