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Hypoxia inducible factor‐1 alpha plays a pivotal role in hepatic metastasis of pancreatic cancer: an immunohistochemical study
Author(s) -
Matsuo Yoichiro,
Ding Qiang,
Desaki Ryosuke,
Maemura Kosei,
Mataki Yuko,
Shinchi Hiroyuki,
Natsugoe Shoji,
Takao Sonshin
Publication year - 2014
Publication title -
journal of hepato‐biliary‐pancreatic sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.63
H-Index - 60
eISSN - 1868-6982
pISSN - 1868-6974
DOI - 10.1002/jhbp.6
Subject(s) - immunohistochemistry , angiogenesis , hif1a , metastasis , hypoxia inducible factors , microvessel , vascular endothelial growth factor , pancreatic cancer , medicine , hypoxia (environmental) , thymidine phosphorylase , pathology , basic fibroblast growth factor , cancer research , cancer , oncology , growth factor , biology , chemistry , vegf receptors , receptor , biochemistry , organic chemistry , oxygen , gene
Background Hypoxia is an important condition to promote angiogenesis that is essential to tumor progression, including pancreatic ductal adenocarcinoma ( PDAC ). We evaluated whether the immunohistochemistry for hypoxia inducible factor‐1α ( HIF ‐1α) was correlated with hepatic metastases in PDAC . Methods We examined the expression of HIF ‐1α, vascular endothelial growth factor‐ A ( VEGF ‐ A ), thymidine phosphorylase ( TP ) and basic fibroblast growth factor ( bFGF ) in a total of 100 paraffin‐embedded PDAC primary tumors using immunohistochemical staining, and assessed their clinicopathological correlations. We determined microvessel count ( MVC ) and apoptotic index ( AI ), and assessed their correlations with hepatic metastases. Student's t ‐test, the M ann– W hitney U ‐test, and S pearman correlation coefficients were used to validate the model, and regression analysis was used to test the model. Results Hypoxia inducible factor‐1α expression induced the expression of multiple angiogenic factors, leading to a higher MVC and a lower AI . HIF ‐1α expression ( P = 0.0087) and angiogenic factors ( P = 0.0079) were significantly associated with not only the microvessel status ( P = 0.022) but also the high incidence of hepatic metastasis ( P = 0.02), resulting in the worse survival of PDAC patients ( P < 0.05). Conclusions Hypoxia inducible factor‐1α plays a pivotal role in hepatic metastasis through its association with the expression of angiogenic factors in PDAC patients. These results may contribute future therapeutic strategies to prevent pancreatic cancer metastasis.