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


Takuya Kitada MD, PhD, Third Department of Internal Medicine, Osaka City University Medical School, 1-4-3, Asahimachi, Abenoku, Osaka 545-8585, Japan.


Aims:  The transcription factor hypoxia-inducible factor-1α (HIF-1α) 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-1α expression in pancreatic carcinoma.

Methods and results:  We investigated HIF-1α expression immunohistochemically in pancreatic carcinoma tissues and regional lymph node metastasis. In cases of pancreatic ductal carcinoma, the relationship between HIF-1α expression and various clinicopathological parameters including cellular proliferation, apoptosis, and microvessel density, was also examined. Over-expression of HIF-1α 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-1α expression was almost absent in non-cancerous pancreatic tissues. HIF-1α 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-1α expression positively correlated with cellular proliferation (P = 0.024) and microvessel density/neo-angiogenesis (P = 0.038), but not with apoptosis.

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