Promoter methylation of CDKN2A and lack of p16 expression characterize patients with hepatocellular carcinoma
<p>Abstract</p> <p>Background</p> <p>The product of CDKN2A, p16 is an essential regulator of the cell cycle controlling the entry into the S-phase. Herein, we evaluated CDKN2A promoter methylation and p16 protein expression for the differentiation of hepatocellular carc...
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| Format: | Article |
| Language: | English |
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BMC
2010-06-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/10/317 |
| _version_ | 1811286310743179264 |
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| author | Schneider-Stock Regine Röcken Christoph Ebert Matthias PA Csepregi Antal Hoffmann Juliane Schulz Hans-Ulrich Roessner Albert Malfertheiner Peter |
| author_facet | Schneider-Stock Regine Röcken Christoph Ebert Matthias PA Csepregi Antal Hoffmann Juliane Schulz Hans-Ulrich Roessner Albert Malfertheiner Peter |
| author_sort | Schneider-Stock Regine |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The product of CDKN2A, p16 is an essential regulator of the cell cycle controlling the entry into the S-phase. Herein, we evaluated CDKN2A promoter methylation and p16 protein expression for the differentiation of hepatocellular carcinoma (HCC) from other liver tumors.</p> <p>Methods</p> <p>Tumor and corresponding non-tumor liver tissue samples were obtained from 85 patients with liver tumors. CDKN2A promoter methylation was studied using MethyLight technique and methylation-specific PCR (MSP). In the MethyLight analysis, samples with ≥ 4% of PMR (percentage of methylated reference) were regarded as hypermethylated. p16 expression was evaluated by immunohistochemistry in tissue sections (n = 148) obtained from 81 patients using an immunoreactivity score (IRS) ranging from 0 (no expression) to 6 (strong expression).</p> <p>Results</p> <p>Hypermethylation of the CDKN2A promoter was found in 23 HCCs (69.7%; mean PMR = 42.34 ± 27.8%), six (20.7%; mean PMR = 31.85 ± 18%) liver metastases and in the extralesional tissue of only one patient. Using MSP, 32% of the non-tumor (n = 85), 70% of the HCCs, 40% of the CCCs and 24% of the liver metastases were hypermethylated. Correspondingly, nuclear p16 expression was found immunohistochemically in five (10.9%, mean IRS = 0.5) HCCs, 23 (92%; mean IRS = 4.9) metastases and only occasionally in hepatocytes of non-lesional liver tissues (mean IRS = 1.2). The difference of CDKN2A-methylation and p16 protein expression between HCCs and liver metastases was statistically significant (p < 0.01, respectively).</p> <p>Conclusion</p> <p>Promoter methylation of CDKN2A gene and lack of p16 expression characterize patients with HCC.</p> |
| first_indexed | 2024-04-13T02:57:47Z |
| format | Article |
| id | doaj.art-7453412545d84c08801b17bb4d5bdfd4 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-13T02:57:47Z |
| publishDate | 2010-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-7453412545d84c08801b17bb4d5bdfd42022-12-22T03:05:33ZengBMCBMC Cancer1471-24072010-06-0110131710.1186/1471-2407-10-317Promoter methylation of CDKN2A and lack of p16 expression characterize patients with hepatocellular carcinomaSchneider-Stock RegineRöcken ChristophEbert Matthias PACsepregi AntalHoffmann JulianeSchulz Hans-UlrichRoessner AlbertMalfertheiner Peter<p>Abstract</p> <p>Background</p> <p>The product of CDKN2A, p16 is an essential regulator of the cell cycle controlling the entry into the S-phase. Herein, we evaluated CDKN2A promoter methylation and p16 protein expression for the differentiation of hepatocellular carcinoma (HCC) from other liver tumors.</p> <p>Methods</p> <p>Tumor and corresponding non-tumor liver tissue samples were obtained from 85 patients with liver tumors. CDKN2A promoter methylation was studied using MethyLight technique and methylation-specific PCR (MSP). In the MethyLight analysis, samples with ≥ 4% of PMR (percentage of methylated reference) were regarded as hypermethylated. p16 expression was evaluated by immunohistochemistry in tissue sections (n = 148) obtained from 81 patients using an immunoreactivity score (IRS) ranging from 0 (no expression) to 6 (strong expression).</p> <p>Results</p> <p>Hypermethylation of the CDKN2A promoter was found in 23 HCCs (69.7%; mean PMR = 42.34 ± 27.8%), six (20.7%; mean PMR = 31.85 ± 18%) liver metastases and in the extralesional tissue of only one patient. Using MSP, 32% of the non-tumor (n = 85), 70% of the HCCs, 40% of the CCCs and 24% of the liver metastases were hypermethylated. Correspondingly, nuclear p16 expression was found immunohistochemically in five (10.9%, mean IRS = 0.5) HCCs, 23 (92%; mean IRS = 4.9) metastases and only occasionally in hepatocytes of non-lesional liver tissues (mean IRS = 1.2). The difference of CDKN2A-methylation and p16 protein expression between HCCs and liver metastases was statistically significant (p < 0.01, respectively).</p> <p>Conclusion</p> <p>Promoter methylation of CDKN2A gene and lack of p16 expression characterize patients with HCC.</p>http://www.biomedcentral.com/1471-2407/10/317 |
| spellingShingle | Schneider-Stock Regine Röcken Christoph Ebert Matthias PA Csepregi Antal Hoffmann Juliane Schulz Hans-Ulrich Roessner Albert Malfertheiner Peter Promoter methylation of CDKN2A and lack of p16 expression characterize patients with hepatocellular carcinoma BMC Cancer |
| title | Promoter methylation of CDKN2A and lack of p16 expression characterize patients with hepatocellular carcinoma |
| title_full | Promoter methylation of CDKN2A and lack of p16 expression characterize patients with hepatocellular carcinoma |
| title_fullStr | Promoter methylation of CDKN2A and lack of p16 expression characterize patients with hepatocellular carcinoma |
| title_full_unstemmed | Promoter methylation of CDKN2A and lack of p16 expression characterize patients with hepatocellular carcinoma |
| title_short | Promoter methylation of CDKN2A and lack of p16 expression characterize patients with hepatocellular carcinoma |
| title_sort | promoter methylation of cdkn2a and lack of p16 expression characterize patients with hepatocellular carcinoma |
| url | http://www.biomedcentral.com/1471-2407/10/317 |
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