Abstract
Purpose: The tumor suppressor gene p16INK4A is mainly inactivated by an epigenetic change involving promoter hypermethylation in hepatocarcinogenesis. The possible clinical impact of p16INK4A methylation and the potential risk factors for this epigenetic alteration have not been thoroughly investigated. Experimental Design: We studied the methylation status and mRNA and protein expression of p16INK4A in 50 hepatocellular carcinomas and corresponding nonneoplastic liver lesions using methylation-specific PCR, reverse transcription-PCR, and immunohistochemical techniques. Results: p16INK4A hypermethylation was observed in 58% (29 of 50) of the hepatocellular carcinomas and 16% (6 of 38) of the corresponding chronic hepatitis and cirrhosis tissue samples. p16 INK4A methylation was significantly associated with mRNA and protein expression (P <0.001 and P = 0.003, respectively). All of the p16 INK4A-methylated tumors were positive for hepatitis B virus or hepatitis C virus markers, but none of the virus-negative tumors exhibited p16INK4A methylation (P = 0.006). The frequency of p16 INK4A hypermethylation tended to be higher in hepatitis C virus-related tumors (23 of 32, 72%) than in hepatitis B virus-related tumors (6 of 13, 46%; P = 0.1). Aberrant methylation of p16INK4A was also related significantly to increasing age, female gender, and normal levels of serum PIVKA-II (P = 0.02, 0.04, and 0.04, respectively). No statistically significant difference in survival was observed between patients with p16 INK4A hypermethylation and those without. Conclusions: Our observations suggest that p16INK4A hypermethylation may contribute to hepatocarcinogenesis from an early stage and that multiple risk factors, such as viral infections, age, and gender, may be associated with p16INK4A hypermethylation in hepatocarcinogenesis.
| Original language | English |
|---|---|
| Pages (from-to) | 7484-7489 |
| Number of pages | 6 |
| Journal | Clinical Cancer Research |
| Volume | 10 |
| Issue number | 22 |
| DOIs | |
| Publication status | Published - Dec 15 2004 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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p16INK4A hypermethylation is associated with hepatitis virus infection, age, and gender in hepatocellular carcinoma. / Li, Xin; Hei, Ai Min; Sun, Lin; Hasegawa, Kiyoshi; Torzilli, Guido; Minagawa, Masami; Takayama, Tadatoshi; Makuuchi, Masatoshi.
In: Clinical Cancer Research, Vol. 10, No. 22, 15.12.2004, p. 7484-7489.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - p16INK4A hypermethylation is associated with hepatitis virus infection, age, and gender in hepatocellular carcinoma
AU - Li, Xin
AU - Hei, Ai Min
AU - Sun, Lin
AU - Hasegawa, Kiyoshi
AU - Torzilli, Guido
AU - Minagawa, Masami
AU - Takayama, Tadatoshi
AU - Makuuchi, Masatoshi
PY - 2004/12/15
Y1 - 2004/12/15
N2 - Purpose: The tumor suppressor gene p16INK4A is mainly inactivated by an epigenetic change involving promoter hypermethylation in hepatocarcinogenesis. The possible clinical impact of p16INK4A methylation and the potential risk factors for this epigenetic alteration have not been thoroughly investigated. Experimental Design: We studied the methylation status and mRNA and protein expression of p16INK4A in 50 hepatocellular carcinomas and corresponding nonneoplastic liver lesions using methylation-specific PCR, reverse transcription-PCR, and immunohistochemical techniques. Results: p16INK4A hypermethylation was observed in 58% (29 of 50) of the hepatocellular carcinomas and 16% (6 of 38) of the corresponding chronic hepatitis and cirrhosis tissue samples. p16 INK4A methylation was significantly associated with mRNA and protein expression (P <0.001 and P = 0.003, respectively). All of the p16 INK4A-methylated tumors were positive for hepatitis B virus or hepatitis C virus markers, but none of the virus-negative tumors exhibited p16INK4A methylation (P = 0.006). The frequency of p16 INK4A hypermethylation tended to be higher in hepatitis C virus-related tumors (23 of 32, 72%) than in hepatitis B virus-related tumors (6 of 13, 46%; P = 0.1). Aberrant methylation of p16INK4A was also related significantly to increasing age, female gender, and normal levels of serum PIVKA-II (P = 0.02, 0.04, and 0.04, respectively). No statistically significant difference in survival was observed between patients with p16 INK4A hypermethylation and those without. Conclusions: Our observations suggest that p16INK4A hypermethylation may contribute to hepatocarcinogenesis from an early stage and that multiple risk factors, such as viral infections, age, and gender, may be associated with p16INK4A hypermethylation in hepatocarcinogenesis.
AB - Purpose: The tumor suppressor gene p16INK4A is mainly inactivated by an epigenetic change involving promoter hypermethylation in hepatocarcinogenesis. The possible clinical impact of p16INK4A methylation and the potential risk factors for this epigenetic alteration have not been thoroughly investigated. Experimental Design: We studied the methylation status and mRNA and protein expression of p16INK4A in 50 hepatocellular carcinomas and corresponding nonneoplastic liver lesions using methylation-specific PCR, reverse transcription-PCR, and immunohistochemical techniques. Results: p16INK4A hypermethylation was observed in 58% (29 of 50) of the hepatocellular carcinomas and 16% (6 of 38) of the corresponding chronic hepatitis and cirrhosis tissue samples. p16 INK4A methylation was significantly associated with mRNA and protein expression (P <0.001 and P = 0.003, respectively). All of the p16 INK4A-methylated tumors were positive for hepatitis B virus or hepatitis C virus markers, but none of the virus-negative tumors exhibited p16INK4A methylation (P = 0.006). The frequency of p16 INK4A hypermethylation tended to be higher in hepatitis C virus-related tumors (23 of 32, 72%) than in hepatitis B virus-related tumors (6 of 13, 46%; P = 0.1). Aberrant methylation of p16INK4A was also related significantly to increasing age, female gender, and normal levels of serum PIVKA-II (P = 0.02, 0.04, and 0.04, respectively). No statistically significant difference in survival was observed between patients with p16 INK4A hypermethylation and those without. Conclusions: Our observations suggest that p16INK4A hypermethylation may contribute to hepatocarcinogenesis from an early stage and that multiple risk factors, such as viral infections, age, and gender, may be associated with p16INK4A hypermethylation in hepatocarcinogenesis.
UR - http://www.scopus.com/inward/record.url?scp=21644473614&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=21644473614&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-04-1715
DO - 10.1158/1078-0432.CCR-04-1715
M3 - Article
C2 - 15569978
AN - SCOPUS:21644473614
VL - 10
SP - 7484
EP - 7489
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 22
ER -