Quantitative analysis of heparanase gene expression in esophageal squamous cell carcinoma

Ann Surg Oncol. 2003 Apr;10(3):297-304. doi: 10.1245/aso.2003.05.022.


Background: Heparan sulfate proteoglycans, the main components of the extracellular matrix, are recognized as important components of signal transduction and play an important role in tumor progression. Heparanase (hep) degrades heparan sulfate proteoglycans, but the clinical importance of hep is unclear. In this study, we investigated the clinicopathologic importance of hep messenger RNA (mRNA) expression in esophageal squamous cell carcinoma (ESCC).

Methods: Fresh tumors and noncancerous epithelia were obtained from 57 ESCC patients after esophagectomy. Expression levels of hep and glyceraldehyde-3-phosphate dehydrogenase mRNA were quantitatively analyzed by real-time reverse transcriptase-polymerase chain reaction. Apoptotic cancer cells and microvessel density were evaluated immunohistochemically.

Results: The relative hep mRNA expression level (hep:glyceraldehyde-3-phosphate dehydrogenase ratio) in ESCC was lower than in noncancerous tissue (P <.001). Tumor hep expression decreased according to tumor progression and correlated with the occurrence of apoptotic cancer cells, but not with tumor microvessel density. Moreover, low hep expression correlated with poor patient survival.

Conclusions: Reduced hep mRNA expression might result in abnormal cell growth and correlate with ESCC progression.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / surgery
  • Cell Division
  • Disease Progression
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology*
  • Esophageal Neoplasms / surgery
  • Esophagectomy
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glucuronidase / analysis
  • Glucuronidase / biosynthesis*
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival


  • RNA, Messenger
  • heparanase
  • Glucuronidase