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Promoter hypermethylation of tumor suppressor genes is a common feature of primary cancer cells. However, at date the somatic epigenetic events that occur in head and neck squamous cell carcinoma (HNSCC) tumorigenesis are not yet been well defined. In the present study we analysed the methylation status of the gene hypermethylated in cancer-1 (hic1), a gene located on chromosome 17p13.3, a region frequently lost in HNSCC. We analysed 22 HNSCC samples and three cell lines using methylation specific PCR (MSP). We found hic1 methylated in 21 out of 22 samples and in all three cell lines. Treatment of the cell lines with the demethylating agent 5-Azacytidin (5-Aza) resulted in the demethylation of the hic1 promoter and reactivation of hic1 expression as determined by MSP, qPCR and Western blot. Functional analyses revealed decreased proliferative activity and colony forming ability of treated cells. In summary, we found in HNSCC hic1 regulated by promoter methylation. 5-Aza application resulted in the reexpression of hic1 and was followed by decreased aggressiveness of the cancer cells. Our data indicate that hic1 might be a player in HNSCC development and suggest further evaluation of 5-Aza for HNSCC treatment., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Costimulatory molecules have complementary effects on T-cell activation and their balance may control the development of oral cancer. The aim of this study was to determine the relevance of cytotoxic T-lymphocyte antigen 4 (CTLA-4), CD28 and inducible costimulator (ICOS) polymorphisms in oral squamous cell carcinoma (OSCC). Genotyping for CTLA-4 (-1661 A/G and +49 A/G), CD28 (0 C/G and +3160 G/T) and ICOS (+637 A/C and +1599 C/T) was performed in the 83 patients with OSCC, compared to the 40 unrelated healthy volunteers as controls. The genotype CTLA-4 -1661 was significantly different between the patient group and the control group. The allele CTLA-4 -1661 G was significantly found more frequent in patients with OSCC (p=0.001). In bivariate analysis, noticeable differences between OSCC and controls were seen. The combinations CTLA-4 -1661 G/G and CTLA-4 +49 A/G, ICOS +1559 C/T and ICOS +1559 C/C each with CTLA-4 -1661 G/G, ICOS +637 C/C and ICOS +637 A/C each with CTLA-4 -1661, CTLA-4 -1661 A/G and ICOS +637 C/C, CD28 +3160 G/T and CTLA-4 -1661 A/A and CD28 +3160 G/T and CTLA-4 -1661 A/G were seen in the patient group only. Especially the polymorphisms of the CTLA-4 -1661-genotype - alone and in combination with other T cell regulator polymorphisms - seem to be possible predisposing factors for OSCC. Therefore, they might be future targets for a primary prophylaxis or an individualised therapy.