[Expression and clinical significance of hypoxia-inducible factor-1alpha and cyclooxygenase-2 in laryngeal squamous cell carcinoma].
OBJECTIVE
To investigate the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and cyclooxygenase-2 (COX-2) in laryngeal squamous cell carcinoma (LSCC), while determine their relationship with clinicopathologic characteristics and prognosis.


METHODS
Tumor tissues were obtained from 60 patients who underwent resection of laryngeal carcinoma in Affiliated First People's Hospital of Shanghai Jiaotong University. Immunohistochemistry (Envision DAKO) was used to detect the expressions of HIF-1alpha and COX-2 in the tumor tissues. As control group, 15 cases of atypical hyperplasia, 10 cases of leukoplakia of vocal cord and 10 cases of polyp of vocal cord were studied. All patients were regularly followed up and the clinical data were collected systematically.


RESULTS
Positive staining rates of HIF-1alpha and COX-2 were 95.0% (57/60) and 98.3% (59/60), respectively in all 60 specimen of LSCC. The positive expressions in LSCC were significantly higher than those in atypical hyperplasia, leukoplakia and polyp of vocal cord ( Fisher's exact test, P < 0.01). The expression of HIF-1alpha was correlated with COX-2 in LSCC (r = 0.526, P < 0.01). High level expressions of HIF-1alpha and COX-2 were 35.0% (21/60) and 38.3% (23/60) respectively. High level expression of HIF-1alpha was significantly correlated with clinical stages (chi2 = 4.331, P < 0.05) and lymph nodes metastases (Fisher's exact test, P < 0.05). High level expression of COX-2 was significantly correlated with clinical stage (chi2 = 8.539, P < 0.01) and T stages (chi2 = 6.792, P < 0.01). With univariate analysis, high level expressions of HIF-1alpha and COX-2 were significantly associated with a worse overall survival (chi2 = 6.003, P < 0.05 and chi2 = 9.489, P < 0.01, respectively) and disease-free survival (chi2 = 5.010, P < 0.05 and chi2 = 6.102, P < 0.05, respectively). With multivariate analysis, recurrence and high level expression of COX-2 were two unfavorable prognostic factors (RR = 7.104, P = 0.003; RR = 5.714, P = 0.008).


CONCLUSIONS
The expressions of HIF-1alpha and COX-2 played an important role in the process of tumorigenesis and development of LSCC, The expression of HIF-1alpha was correlated with COX-2 in LSCC. COX-2 and recurrence were probably significant risk factors for prognosis of LSCC.
Xu
Cheng-zhi
CZ
Department of Otorhinolaryngology Head and Neck Surgery, Affiliated First People's Hospital of Shanghai Jiaotong University, Shanghai 200080, China.
Dong
Pin
P
Li
Xiao-yan
XY
Zhang
Zhi-jie
ZJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human