PAI-1, CAIX, and VEGFA expressions as prognosis markers in oral squamous cell carcinoma

J Oral Pathol Med. 2018 Jul;47(6):566-574. doi: 10.1111/jop.12721. Epub 2018 May 15.

Abstract

Background: In oral squamous cell carcinoma (OSCC), the HIF-1 complex promotes the expression of genes involved in specific mechanisms of cell survival under hypoxic conditions, such as plasminogen activator inhibitor-1 (PAI-1), carbonic anhydrase 9 (CAIX), and vascular endothelial growth factor A (VEGFA). The study aimed to investigate the presence and prognostic value of PAI-1, CAIX, and VEGFA in OSCC.

Materials and methods: Immunohistochemistry was used to analyze the expressions of these proteins in 52 tumoral tissue samples of patients with OSCC, surgically treated and followed by a minimum of 24 months after surgery. The correlations between protein expressions and clinicopathological parameters and prognosis were analyzed.

Results: Positive PAI-1 membrane expression was significantly associated with local disease relapse (P = .027). Multivariate analysis revealed that the positive PAI-1 membrane expression is an independent marker for local disease relapse, with approximately 14-fold increased risk when compared to negative expression (OR = 14.49; CI = 1.40-150.01, P = .025). Strong PAI-1 cytoplasmic expression was significantly associated with the less differentiation grade (P = .027). Strong CAIX membrane expression was significantly associated with local disease-free survival (P = .038). Positive CAIX cytoplasmic expression was significantly associated with lymph node affected (P = .025) and with disease-specific survival (P = .022). Multivariate analysis revealed that the positive CAIX cytoplasmic expression is an independent risk factor for disease-related death, increasing their risk approximately 3-fold when compared to negative expression (HR = 2.84; CI = 1.02-7.87, P = .045). Positive VEGFA cytoplasmic expression was significantly associated with less differentiation grade (P = .035).

Conclusion: Our results suggest a potential role for these expressions profiles as tumor prognostic markers in OSCC patients.

Keywords: CAIX; PAI-1; VEGFA; hypoxia; oral squamous cell carcinoma.

MeSH terms

  • Aged
  • Antigens, Neoplasm / biosynthesis*
  • Antigens, Neoplasm / metabolism
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / metabolism
  • Carbonic Anhydrase IX / biosynthesis*
  • Carbonic Anhydrase IX / metabolism
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Lymph Nodes / pathology
  • Male
  • Middle Aged
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Multivariate Analysis
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Plasminogen Activator Inhibitor 1 / biosynthesis*
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Prognosis
  • Squamous Cell Carcinoma of Head and Neck / metabolism*
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Survival Analysis
  • Vascular Endothelial Growth Factor A / biosynthesis*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • CA9 protein, human
  • Carbonic Anhydrase IX