BMC Cancer (Jun 2010)

Promoter methylation of CDKN2A and lack of p16 expression characterize patients with hepatocellular carcinoma

  • Schneider-Stock Regine,
  • Röcken Christoph,
  • Ebert Matthias PA,
  • Csepregi Antal,
  • Hoffmann Juliane,
  • Schulz Hans-Ulrich,
  • Roessner Albert,
  • Malfertheiner Peter

DOI
https://doi.org/10.1186/1471-2407-10-317
Journal volume & issue
Vol. 10, no. 1
p. 317

Abstract

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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 Conclusion Promoter methylation of CDKN2A gene and lack of p16 expression characterize patients with HCC.