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

Csepregi, A; Ebert, MP; Röcken, C; Schneider-Stock, R; Hoffmann, J; Schulz, HU; Roessner, A; Malfertheiner, P

doi:10.1186/1471-2407-10-317

journal article

Titel:: Promoter methylation of CDKN2A and lack of p16 expression characterize patients with hepatocellular carcinoma.
Dokumenttyp:: Journal Article; Article
Autor(en):: Csepregi, A; Ebert, MP; Röcken, C; Schneider-Stock, R; Hoffmann, J; Schulz, HU; Roessner, A; Malfertheiner, P
Abstract:: 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.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 > or = 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).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).Promoter methylation of CDKN2A gene and lack of p16 expression characterize patients with HCC.
Zeitschriftentitel:: BMC Cancer
Jahr:: 2010
Band / Volume:: 10
Seitenangaben Beitrag:: 317
Sprache:: eng
Volltext / DOI:: doi:10.1186/1471-2407-10-317
PubMed:: http://view.ncbi.nlm.nih.gov/pubmed/20569442
TUM Einrichtung:: II. Medizinische Klinik und Poliklinik (Gastroenterologie)
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Klinik und Poliklinik für Innere Medizin II, Gastroenterologie (Prof. Schmid)2010