Levels and patterns of expression of hypoxia-inducible factor-1α, vascular endothelial growth factor, glucose transporter-1 and CD105 in adenoid cystic carcinomas with high-grade transformation

Histopathology. 2012 Apr;60(5):816-25. doi: 10.1111/j.1365-2559.2011.04128.x. Epub 2012 Feb 9.

Abstract

Aims: To compare the expression of proteins regulated by hypoxia between adenoid cystic carcinoma (ACC) with and without high-grade transformation (HGT).

Methods and results: In eight ACC-HGT and 18 ACC without HGT, expression of hypoxia-inducible factor-1 (HIF-1α), vascular endothelial growth factor (VEGF), glucose transporter-1 (GLUT-1) and microvascular density (MVD) by CD105 (a hypoxia-inducible protein expressed in angiogenic endothelial cells) was determined. Expression levels of HIF-1α and VEGF as well as CD105-MVD did not differ significantly between: (i) transformed and conventional areas (TA and CA, respectively) of ACC-HGT, (ii) CA and ordinary ACC. HIF-1α was detected in 100% of cases and presented a diffuse expression pattern. No significant association was found between levels of HIF-1α expression and tumour size, metastasis and recurrence. GLUT-1 showed a prostromal expression pattern and was observed exclusively in TA (three of six cases) and in only three of 14 ACC.

Conclusions: Both the absence of significant alterations in levels of expression of HIF-1α, VEGF and CD105 and the patterns of expression of HIF-1α and GLUT-1 suggest that hypoxia may not play a key role in the process of high-grade transformation of ACC. Although HIF-1α expression is a common finding in ACC, it cannot be used as a marker of tumour aggressiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Adenoid Cystic / metabolism*
  • Carcinoma, Adenoid Cystic / mortality
  • Carcinoma, Adenoid Cystic / therapy
  • Cell Transformation, Neoplastic / pathology*
  • Combined Modality Therapy
  • Endoglin
  • Female
  • Glucose Transporter Type 1 / metabolism*
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / therapy
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Male
  • Middle Aged
  • Receptors, Cell Surface / metabolism*
  • Survival Rate
  • Vascular Endothelial Growth Factor A / metabolism*
  • Young Adult

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • ENG protein, human
  • Endoglin
  • Glucose Transporter Type 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Receptors, Cell Surface
  • Vascular Endothelial Growth Factor A