FOXA1 in HPV associated carcinomas: Its expression in carcinomas of the head and neck and of the uterine cervix

Exp Mol Pathol. 2017 Apr;102(2):230-236. doi: 10.1016/j.yexmp.2017.02.010. Epub 2017 Feb 14.

Abstract

Background: FOXA1 is a major transcription factor involved in the action of human papilloma virus (HPV). However, it has been never studied in HPV-associated tumors.

Aim of the study: To investigate its expression in cervical and head and neck tumors.

Material and methods: 63 cervical carcinomas/dysplasias and 152 head and neck squamous cell carcinomas (HNSCC) were immunohistochemically studied for the expression of FOXA1.

Results: 63.1% of cervical SCC and 40.7% of endocervical adenocarcinomas strongly expressed FOXA1. Most (90%) pre-invasive lesions (CIN3 and in situ adenocarcinomas) strongly expressed FOXA1 and this difference from invasive lesions was statistically significant (p=0.005). No association with clinicopathological factors was found. 51.3% of HNSCC expressed FOXA1. In these tumors, FOXA1 expression was associated with the non-keratinizing morphology but not with the HPV/p16 status neither other clinicopathological features. Of normal structures, salivary glands, endocervical glands and basal/parabasal cell layer of squamous epithelium of both uterine cervix and head and neck mucosa, all strongly expressed FOXA1.

Conclusion: FOXA1 is expressed by basal cells of squamous epithelium, pre-invasion lesions of the uterine cervix and the head/neck and almost half invasive cervical and head/neck carcinomas, supporting its possible implication in HPV pathogenesis.

Keywords: Carcinogenesis; Cervix; Dysplasia; FOXA1; HPV; Oropharynx; Tumor.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / virology
  • Cervix Uteri / pathology
  • Cervix Uteri / virology*
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / virology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / virology
  • Hepatocyte Nuclear Factor 3-alpha / genetics
  • Hepatocyte Nuclear Factor 3-alpha / metabolism*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Papillomaviridae
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / pathology
  • Squamous Cell Carcinoma of Head and Neck
  • Uterine Cervical Dysplasia / genetics*
  • Uterine Cervical Dysplasia / virology

Substances

  • FOXA1 protein, human
  • Hepatocyte Nuclear Factor 3-alpha