gms | German Medical Science

83rd Annual Meeting of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery

German Society of Oto-Rhino-Laryngology, Head and Neck Surgery

16.05. - 20.05.2012, Mainz

Epigenetic and translational modifications of Transcription Factor 21 are associated with Head and Neck Squamous Cell Carcinoma

Meeting Abstract

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German Society of Oto-Rhino-Laryngology, Head and Neck Surgery. 83rd Annual Meeting of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery. Mainz, 16.-20.05.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12hno25

DOI: 10.3205/12hno25, URN: urn:nbn:de:0183-12hno255

Published: July 23, 2012

© 2012 Weiss et al.
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Outline

Text

Epigenetic alterations, especially promoter methylation, of Transcription Factor 21 (TCF21) could be associated with Head and Neck Squamous Cell Carcinoma (HNSCC) development by our research group and others. This time we intended to gather information about the influence of promoter methylation of TCF21 on its protein expression. Furthermore, we were interested in the relations of TCF21 expression with clinicopathological parameters.

We therefore screened formalin-fixed paraffin embedded tissue sections of 77 HNSCC and 31 benign tonsils for TCF21 protein expression and correlated it to the methylation status of TCF21, patients’ history and pathological findings. Protein expression of TCF21 was analyzed with abcam antibody ab32981. Promoter methylation status of TCF21 was analyzed with the Methyl-Profiler™ DNA Methylation PCR Array System (SABiosciences, Frederick, USA).

The protein expression rate of TCF21 in benign tonsils never reached levels above 1%. For this reason and because of lacking information in literature we decided to adjust the cut off level for considering a TCF21 overexpression at ≥ 10% positive cells. Statistical analyses were performed using SigmaPlot Software. The clinical and pathological data was analyzed by Fisher’s exact test for categorical variables and Mann-Whitney test for continuous variables. Possible correlation between two continuous variables was analyzed by Spearman rank order. Differences in survival probability were compared by Kaplan-Meier LogRank, whereby death from any cause was considered an event and data on patients who were alive at the last follow-up contact were censored.

Expression rates of TCF21 in HNSCC were much higher than in tonsils (p<0.001). In HNSCC methylation of TCF21 predicted lower expression rates (p=0.037). Tumors of the anterior two thirds of the tongue showed higher expression rates than tumors of other subsites (p=0.029). Tumors of patients with nicotine and alcohol abuse showed higher expression rates of TCF21 than those of patients without nicotine and alcohol abuse (p=0.059 and p=0.038). Interestingly, we could detect lower TCF21 expression in Human Papillomavirus 16 (HPV16) positive tumors (p=0.060). We also examined blood vessel density by immunohistochemical analysis of CD31 expression, a marker for endothelial cells. Expression of CD31 was negatively correlated with expression of TCF21 (p=0.041).

Taken together our results indicate a clear link between epigenetic and translational modifications of TCF21 and HNSCC development. Both, enhanced promoter methylation and increased protein expression, are frequent events in HNSCC. Comparing the currently existing two models of HNSCC development, namely the one induced by high-risk HPV and the one induced by consumption of nicotine and alcohol, we would assign the epigenetic and translational modifications of TCF21 to the latter model.


References

1.
Weiss D, Basel T, Sachse F, Braeuninger A, Rudack C. Promoter methylation of cyclin A1 is associated with human papillomavirus 16 induced head and neck squamous cell carcinoma independently of p53 mutation. Mol Carcinog. 2011;50(9):680-8.
2.
Smith LT, Lin M, Brena RM, Lang JC, Schuller DE, Otterson GA, Morrison CD, Smiraglia DJ, Plass C. Epigenetic regulation of the tumor suppressor gene TCF21 on 6q23-q24 in lung and head and neck cancer. Proc Natl Acad Sci U S A. 2006;103(4):982-7.