Dysregulation of ß-catenin, WISP1 and TCF21 predicts disease-specific survival and primary response against radio(chemo)therapy in patients with locally advanced squamous cell carcinomas of the head and neck

Clin Otolaryngol. 2019 May;44(3):263-272. doi: 10.1111/coa.13281. Epub 2019 Feb 5.

Abstract

Objective: The objective of this study was to determine the prognostic and predictive impact of β-catenin, TCF21 and WISP1 expression in patients with squamous cell carcinomas of the head and neck who underwent primary radiotherapy or concomitant chemoradiotherapy.

Study design: Prospective cohort study.

Setting: University hospital.

Participants: Protein expression profiles of β-catenin, TCF21, WISP1 and p16 were determined by immunohistochemical analyses in tissue samples of 59 untreated patients. Expression was correlated with different outcome parameters.

Main outcome measures: Impact of TNM classification, grading, sex, age, gender, type of therapy, response to therapy and p16 status on disease-specific (DSS) and disease-free survival (DFS).

Results: Patients with high expression of TCF21 were associated with significantly worse disease-specific survival (P = 0.005). In a multivariable analysis, TCF21 was a significant determinant of disease-specific survival. (HR 3.01; P = 0.036). Conversely, low expression of β-catenin (P = 0.025) and WISP1 (P = 0.037) revealed a better response to radiotherapy.

Conclusion: Since data show that TCF21 is a prognostic factor for disease-specific survival and WISP1 and ß-catenin are predictive factors for clinical outcome after definitive radiotherapy, further studies are warranted to prove these preliminary but very promising findings.

Keywords: TCF21; WISP1; WNT; prognosis; radiotherapy.

MeSH terms

  • Adult
  • Austria / epidemiology
  • Basic Helix-Loop-Helix Transcription Factors / biosynthesis*
  • Biomarkers, Tumor / biosynthesis
  • CCN Intercellular Signaling Proteins / biosynthesis*
  • Chemoradiotherapy
  • Female
  • Follow-Up Studies
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / therapy
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Staging*
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Proto-Oncogene Proteins / biosynthesis*
  • Squamous Cell Carcinoma of Head and Neck / metabolism*
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • Squamous Cell Carcinoma of Head and Neck / therapy
  • Survival Rate / trends
  • beta Catenin / biosynthesis*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers, Tumor
  • CCN Intercellular Signaling Proteins
  • CCN4 protein, human
  • Proto-Oncogene Proteins
  • TCF21 protein, human
  • beta Catenin