Transforming growth factor beta1 (TGFbeta1) expression in head and neck squamous cell carcinoma patients as related to prognosis

J Oral Pathol Med. 2003 Mar;32(3):139-45. doi: 10.1034/j.1600-0714.2003.00012.x.

Abstract

Background: Transforming growth factor beta1 (TGFbeta1) is a negative growth regulator in keratinocytes, and in vitro studies lead to the concept that loss of TGFbeta1 responsiveness is a critical step in epithelial carcinogenesis.

Objective: To investigate the prognostic relevance of TGFbeta1 expression in head and neck squamous cell carcinoma (HNSCC).

Materials and methods: TGFbeta1 distribution was determined by immunohistochemistry in oral cavity/oropharynx (n = 79), larynx (n = 36) and hypopharynx (n = 25) tumors and in matched normal adjacent mucosa. TGFbeta-type I and II receptors were determined in 20 cases of differentiated oral cavity/hypopharynx tumors. Cases were considered positive if displaying reactivity in >10% of the cells.

Results: TGFbeta1-positive expression was found in 47.2% of larynx, 36.7% of oral cavity/oropharynx and in 24% of the hypopharynx tumors. Reactivity in >60% of the cells was displayed only by 11.4% of HNSCC. All normal controls were positive. TGFbeta1-positive expression did not correlate with clinico pathological parameters. An association with differentiation was verified only in oral cavity/oropharynx tumors (P </= 0.001). TGFbeta1 was also not related to 5 years survival (Kaplan-Meier). Strong and diffuse expression of TGFbeta-RII was identified in 19/20 cases regardless of TGFbeta1 immunoreactivity. Out of 17 TGFbeta1-positive oral cavity/oropharynx tumors, only nine expressed TGFbeta-RI suggesting a disruption of the TGFbeta1 pathway. We conclude that TGFbeta1 protein immunostaining is not a useful biomarker in assessment of prognosis in HNSCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors, Type I / analysis
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Carcinoma, Squamous Cell / pathology*
  • Case-Control Studies
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Hypopharyngeal Neoplasms / pathology
  • Immunohistochemistry
  • Laryngeal Neoplasms / pathology
  • Male
  • Middle Aged
  • Mouth Neoplasms / pathology
  • Oropharyngeal Neoplasms / pathology
  • Prognosis
  • Protein Serine-Threonine Kinases / analysis
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / analysis
  • Survival Rate
  • Transforming Growth Factor beta / analysis*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta1

Substances

  • Biomarkers, Tumor
  • Receptors, Transforming Growth Factor beta
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Protein Serine-Threonine Kinases
  • Activin Receptors, Type I
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II