HIF1-alpha overexpression indicates a good prognosis in early stage squamous cell carcinomas of the oral floor.
BACKGROUND
Hypoxia-inducible factor 1 (HIF-1) is a transcription factor, which plays a central role in biologic processes under hypoxic conditions, especially concerning tumour angiogenesis. HIF-1alpha is the relevant, oxygen-dependent subunit and its overexpression has been associated with a poor prognosis in a variety of malignant tumours. Therefore, HIF-1alpha expression in early stage oral carcinomas was evaluated in relation to established clinico-pathological features in order to determine its value as a prognostic marker.


METHODS
85 patients with histologically proven surgically treated T1/2 squamous cell carcinoma (SCC) of the oral floor were eligible for the study. Tumor specimens were investigated by means of tissue micro arrays (TMAs) and immunohistochemistry for the expression of HIF-1. Correlations between clinical features and the expression of HIF-1 were evaluated by Kaplan-Meier curves, log-rank tests and multivariate Cox regression analysis.


RESULTS
HIF-1alpha was frequently overexpressed in a probably non-hypoxia related fashion. The expression of HIF-1alpha was related with a significantly improved 5-year survival rate (p < 0.01) and a significantly increased disease free period (p = 0.01) independent from nodal status and tumour size. In primary node negative T1/T2 SCC of the oral floor, absence of HIF-1alpha expression specified a subgroup of high-risk patients (p < 0.05).


CONCLUSIONS
HIF-1alpha overexpression is an indicator of favourable prognosis in T1 and T2 SCC of the oral floor. Node negative patients lacking HIF-1alpha expression may therefore be considered for adjuvant radiotherapy.
Fillies
Thomas
T
Department of Cranio-Maxillofacial Surgery, University of Münster, Waldeyerstrasse 30, 48129 Münster, Germany. fillies@uni-muenster.de
Werkmeister
Richard
R
van Diest
Paul J
PJ
Brandt
Burkhard
B
Joos
Ulrich
U
Buerger
Horst
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012044:Regression Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit