Overexpression of hypoxia-inducible factor 1alpha and p53 is a marker for an unfavorable prognosis in gastric cancer.
OBJECTIVE
To investigate the effects of the expression of hypoxia-inducible factor 1alpha (HIF-1alpha) and p53 on the prognosis of human gastric cancer, the clinicopathologic characteristics of the tumors and the clinical outcome were analyzed.


METHODS
The expressions of HIF-1alpha and p53 proteins were studied by immunohistochemistry in 216 specimens of primary gastric cancer.


RESULTS
HIF-1alpha(+)/p53(+) tumors more frequently showed an undifferentiated type, an infiltrative growth appearance, and an invasive lymphatic involvement compared with HIF-1alpha(-)/p53(-) tumors. HIF-1alpha(+)/p53(+) tumors also had more lymph node metastasis compared with HIF-1alpha(-)/p53(-) tumors. When stratified for HIF-1alpha and p53 positivity, the patients who were p53-negative and HIF-1alpha-negative had the most favorable prognosis, whereas patients who were p53-positive and HIF-1alpha-positive had the worst prognosis (P=0.0018). Using a multivariate Cox regression analysis, the depth of invasion, lymph node metastasis, and HIF-1alpha positivity were all found to be independent prognostic factors in patients with gastric cancer.


CONCLUSIONS
Thus, HIF-1alpha is considered to be a useful independent prognostic factor in gastric cancer, and the combination of a HIF-1alpha protein overexpression with nonfunctional p53 tends to indicate a dismal prognosis.
Sumiyoshi
Yasushi
Y
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka and Department of Surgery, Saga Prefectural Hospital Koseikan, Saga, Japan.
Kakeji
Yoshihiro
Y
Egashira
Akinori
A
Mizokami
Ken
K
Orita
Hiroyuki
H
Maehara
Yoshihiko
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism; D011379:Prognosis; D012044:Regression Analysis; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis*; D042442:Vascular Endothelial Growth Factors / Q000032:analysis
D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016159:Tumor Suppressor Protein p53; D042442:Vascular Endothelial Growth Factors