Clinical significance of immunohistochemical expression of hypoxia-inducible factor-1alpha as a prognostic marker in rectal adenocarcinoma.
BACKGROUND
Hypoxia-inducible factor-1alpha (HIF-1alpha), a subunit of hypoxia-inducible factor-1 (HIF-1), furnishes tumor cells with the means of adapting to stress parameters, such as tumor hypoxia, and promotes critical steps in tumor progression and aggressiveness by inducing angiogenesis and regulating energy metabolism. In this study, we investigated the relationship between HIF-1alpha and vascular endothelial growth factor (VEGF) and clinicopathologic characteristics, and evaluated the role of HIF-1alpha expression in patients with rectal adenocarcinoma.


METHODS
The immunohistochemical expression of HIF-1alpha and VEGF was evaluated in 30 formalin-fixed, paraffin-embedded postoperative rectal adenocarcinoma tissue samples. Correlations with clinicopathologic characteristics were determined by cross-tabulations. The impact of the immunoreactivity of HIF-1alpha with regard to the overall survival and local control endpoints was determined by univariate analyses.


RESULTS
Increased HIF-1alpha expression was strongly associated with VEGF positivity (P = 0.002), Dukes stage (P = 0.017), and lymph node metastasis (P = 0.001). No correlation was found between the level of HIF-1alpha expression and histologic grade (P = 0.63). The Kaplan-Meier curves showed a significantly shorter overall survival (P = 0.0087) and local control (P = 0.0438) for patients with high HIF-1alpha expression.


CONCLUSIONS
These results show that HIF-1alpha might represent an important biologic marker evaluating the prognosis of patients with rectal adenocarcinoma.
Lu
Xue-guan
XG
Second Hospital Affiliated of Suzhou University, Suzhou, China. luxueguanok@yahoo.com.cn
Xing
Chun-gen
CG
Feng
Yi-zhong
YZ
Chen
Jie
J
Deng
Chong
C
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D015415:Biomarkers; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A