The Role of Increased Connective Tissue Growth Factor in the Pathogenesis of Oral Submucous Fibrosis and its Malignant Transformation-An Immunohistochemical Study

Head Neck Pathol. 2021 Sep;15(3):817-830. doi: 10.1007/s12105-020-01270-9. Epub 2021 Feb 5.

Abstract

Connective tissue growth factor (CTGF), a matricellular protein of the CCN family of extracellular matrix-associated heparin-binding proteins, is highly expressed in various organ fibrosis and several malignant tumors. Although a few studies have been conducted using CTGF in oral submucous fibrosis (OSF) and oral squamous cell carcinoma, no study has demonstrated its relation with various stages of OSF and its malignant transformation. The present study investigated the possible role of CTGF in the pathogenesis of OSF and its malignant transformation by using immunohistochemistry. Ten formalin-fixed paraffin-embedded tissue blocks, each of Stage 1 OSF, Stage 2 OSF, Stage 3 OSF, Stage 4 OSF, well- differentiated squamous cell carcinoma (WDSCC) with OSF and WDSCC without OSF were stained for CTGF by immunohistochemistry. Ten cases of healthy buccal mucosa (NOM) were included as controls. The present study demonstrated a statistically significant expression of CTGF in the epithelium and connective tissue of OSF and WDSCC with and without OSF cases against its complete absence in NOM. We observed an upregulation of CTGF expression from NOM to various stages of OSF to WDSCC with or without OSF. A gradual upregulation of the CTGF expression in various stages of OSF to WDSCC (with and without OSF) against its complete absence in NOM suggests that CTGF plays an important role in the pathogenesis of OSF and its malignant transformation.

Keywords: Connective tissue growth factor (CTGF); Epithelial- mesenchymal transition (EMT); Oral potentially malignant disorder (OPMD); Oral squamous cell carcinoma (OSCC); Oral submucous fibrosis (OSF).

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Connective Tissue Growth Factor / metabolism*
  • Female
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / pathology
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Oral Submucous Fibrosis / metabolism*
  • Oral Submucous Fibrosis / pathology*
  • Squamous Cell Carcinoma of Head and Neck / metabolism
  • Squamous Cell Carcinoma of Head and Neck / pathology*
  • Up-Regulation
  • Young Adult

Substances

  • CCN2 protein, human
  • Connective Tissue Growth Factor