Clinicopathological significance of hypoxia-inducible factor-1alpha expression in human pancreatic carcinoma

Histopathology. 2003 Dec;43(6):550-5. doi: 10.1111/j.1365-2559.2003.01733.x.


Aims: The transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha) plays a key role in the cellular adaptation to hypoxia and the activation of several genes that have been implicated in tumour growth. The aim of this study was to investigate the clinicopathological significance of HIF-1alpha expression in pancreatic carcinoma.

Methods and results: We investigated HIF-1alpha expression immunohistochemically in pancreatic carcinoma tissues and regional lymph node metastasis. In cases of pancreatic ductal carcinoma, the relationship between HIF-1alpha expression and various clinicopathological parameters including cellular proliferation, apoptosis, and microvessel density, was also examined. Over-expression of HIF-1alpha was frequently (29 of 49 cases, 59.2%) detected in pancreatic carcinoma and regional lymph node metastasis (19 of 25 cases, 76.0%), whereas HIF-1alpha expression was almost absent in non-cancerous pancreatic tissues. HIF-1alpha expression was significantly associated with tumour size (P = 0.023) and advanced TNM stage (stage I/II versus stage III, P = 0.039; stage I/II versus stage IV, P = 0.027). Moreover, HIF-1alpha expression positively correlated with cellular proliferation (P = 0.024) and microvessel density/neo-angiogenesis (P = 0.038), but not with apoptosis.

Conclusions: HIF-1alpha may play a critical role in the progression of pancreatic carcinoma.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma, Papillary / metabolism
  • Adenocarcinoma, Papillary / pathology
  • Antigens, CD34 / analysis
  • Apoptosis
  • Blood Vessels / chemistry
  • Blood Vessels / pathology
  • Carcinoma, Acinar Cell / metabolism
  • Carcinoma, Acinar Cell / pathology
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Division
  • Cystadenocarcinoma, Mucinous / metabolism
  • Cystadenocarcinoma, Mucinous / pathology
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Ki-67 Antigen / analysis
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Single-Blind Method
  • Transcription Factors / biosynthesis*


  • Antigens, CD34
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Ki-67 Antigen
  • Transcription Factors