Autor: |
Schneider-Stock Regine, Röcken Christoph, Ebert Matthias PA, Csepregi Antal, Hoffmann Juliane, Schulz Hans-Ulrich, Roessner Albert, Malfertheiner Peter |
Jazyk: |
angličtina |
Rok vydání: |
2010 |
Předmět: |
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Zdroj: |
BMC Cancer, Vol 10, Iss 1, p 317 (2010) |
Druh dokumentu: |
article |
ISSN: |
1471-2407 |
DOI: |
10.1186/1471-2407-10-317 |
Popis: |
Abstract Background 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. Methods 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). Results 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). Conclusion Promoter methylation of CDKN2A gene and lack of p16 expression characterize patients with HCC. |
Databáze: |
Directory of Open Access Journals |
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