Expression of haem oxygenase-1 correlates with tumour aggressiveness and BRAF V600E expression in thyroid cancer

Histopathology. 2015 Feb;66(3):447-56. doi: 10.1111/his.12562. Epub 2014 Nov 25.

Abstract

Aims: Haem oxygenase-1 (HO-1) is an inducible enzyme that participates in haem degradation. Recent studies have indicated that HO-1 activation may play a role in tumour development and progression. The aim of this study was to evaluate the expression of HO-1 in thyroid cancer and its clinicopathological significance.

Methods and results: We observed up-regulation of HO-1 in papillary thyroid tumours in comparison with normal thyroid tissue. Immunohistochemical analysis revealed that 48% of papillary cancers and 36% of follicular cancers, but none of normal thyroid tissues, were positive for HO-1 expression. Among 129 differentiated thyroid cancers, HO-1 expression was associated with patient age (P = 0.001), TNM stage (P = 0.001), and Mayo Clinic metastasis, patient age, completeness of resection, local invasion and tumour size score (P = 0.001). BRAF V600E expression was evaluated immunohistochemically and validated by Sanger sequencing. There was a strong association between HO-1 and BRAF V600E expression in papillary cancers (P = 0.002).

Conclusions: Overexpression of HO-1 in a subset of thyroid cancers is associated with tumour aggressiveness and BRAF V600E expression. HO-1 might have a potential role in prognosis and targeted treatment in patients with thyroid cancer.

Keywords: BRAF; haem oxygenase-1; immunohistochemistry; thyroid cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / analysis*
  • Blotting, Western
  • Female
  • Heme Oxygenase-1 / analysis
  • Heme Oxygenase-1 / biosynthesis*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins B-raf / analysis
  • Proto-Oncogene Proteins B-raf / biosynthesis*
  • Proto-Oncogene Proteins B-raf / genetics
  • Thyroid Neoplasms / pathology*
  • Tissue Array Analysis
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf