[Analysis of HIF-1α and COX-2 expression in tumor stroma and correlation with the degree of neoplasm invasiveness in laryngeal cancer--preliminary study]

Otolaryngol Pol. 2011 Sep;65(5 Suppl):102-8. doi: 10.1016/S0030-6657(11)70717-X.
[Article in Polish]

Abstract

Introduction: Despite extensive research in the field of molecular biology, immunology and histopathology, prognostically unambiguous morphological indicators of the invasiveness of tumor which allow the prediction of disease course in laryngeal cancer have not yet been identified. The aim of this study was to analyze gene and protein expression of HIF-1a and COX-2 in the tumor stroma and to find relationships between clinical and morphological features (pT, G, depth of tumor invasion, plasmalymphocytic infiltration) and certain markers in squamous cell laryngeal carcinoma.

Material and methods: We analyzed a group of 59 patients with verified squamous cell carcinoma of the larynx. The pathological evaluation was included pTNM classification criteria, depth of invasion according to tumor front grading and degree of morphological differentiation. Quantitative analysis of the amplified product in real time (real-time RT2-PCR) for estimation of mRNA HIF-1a and COX-2 expression in tumor cells were used. The level of HIF-1a and COX-2 protein expression by Western blot analysis was determined.

Results: In studied group of laryngeal cancers significant differences in expression of certain molecules analyzed in tumor tissue and noncancerous epithelium of the larynx have been shown. Increased expression of HIF-1a and COX-2 at both mRNA and protein level was indicator of greater aggressiveness of the tumor, evaluated on the basis of clinical and morphological features in laryngeal squamous cell carcinomas. Tumors with the most invasive growth (pT4 stage, low-differentiated tumors G3, neoplastic infiltration with invasion of cartilage of the larynx) had the highest expression of HIF-1a and COX-2 at the mRNA and protein level.

Conclusions: The study pointed out the direction for further research to find unambiguous indicators for estimation of tumor invasiveness and the possibility of practical use of HIF-1a and COX-2 mRNA and protein level assessment as important methods for determining the advancement of clinical and morphological changes in laryngeal cancer, thereby selecting an appropriate model of treatment.

MeSH terms

  • Adult
  • Aged
  • Blotting, Western / methods
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Cyclooxygenase 2 / genetics*
  • Cyclooxygenase 2 / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Staging
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Squamous Cell Carcinoma of Head and Neck
  • Stromal Cells / pathology*

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Messenger
  • Cyclooxygenase 2
  • PTGS2 protein, human