Transforming growth factor beta 1 genotype and p16 as prognostic factors in head and neck squamous cell carcinoma

Acta Otolaryngol. 2012 Sep;132(9):1006-12. doi: 10.3109/00016489.2012.678944. Epub 2012 Jun 5.

Abstract

Conclusion: Transforming growth factor β1 gene (TGFβ1) genotype is a potential p16 independent prognostic factor predicting response to chemoradiotherapy in head and neck squamous cell carcinoma (HNSCC).

Objectives: Expression of p16 and epidermal growth factor receptor (EGFR) has been reported to be associated with survival in HNSCC. We have previously reported that genetic polymorphism of TGFβ1 is linked with survival in HNSCC patients who have undergone chemoradiotherapy. We evaluate here whether TGFB1 genotype can serve as a prognostic factor independent of tumor p16 and EGFR expression.

Methods: Expression of p16 and EGFR was studied by immunohistochemistry in tumors from 130 HNSCC patients. Peripheral blood DNA was used to genotype 95 patients for single nucleotide polymorphism rs1800470 within the TGFβ1 gene. The minimum follow-up time was 31 months.

Results: p16 overexpression was associated with an improved disease-free survival (hazard ratio (HR) = 0.39, 95% CI 0.19-0.78), whereas no evident association was observed between EGFR expression and disease-free survival (HR = 0.90, 95% CI 0.68-1.19). Among the 37 patients who had received chemoradiotherapy, TGFβ1 genotype was associated with disease-free (HR = 0.44, 95% CI 0.19-1.02) and overall survival (HR = 0.31, 95% CI 0.12-0.80) independent of tumor p16 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / therapy
  • Chemoradiotherapy, Adjuvant
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Disease-Free Survival
  • ErbB Receptors / genetics
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Genotype*
  • Humans
  • Male
  • Middle Aged
  • Otorhinolaryngologic Neoplasms / genetics*
  • Otorhinolaryngologic Neoplasms / mortality
  • Otorhinolaryngologic Neoplasms / therapy
  • Polymorphism, Single Nucleotide / genetics
  • Prognosis
  • Transforming Growth Factor beta1 / genetics*

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • Transforming Growth Factor beta1
  • EGFR protein, human
  • ErbB Receptors