Levels of TGF-alpha and EGFR protein in head and neck squamous cell carcinoma and patient survival.
BACKGROUND
The most accurate predictor of disease recurrence in patients treated for head and neck squamous cell carcinoma is, at present, the extent of regional lymph node metastasis. Since elevated levels of epidermal growth factor receptor (EGFR) and of its ligand, transforming growth factor-alpha (TGF-alpha), have been detected in primary tumors of patients with head and neck squamous cell carcinoma, we determined whether tumor levels of these proteins were of prognostic importance.


METHODS
Monoclonal antibodies specific for EGFR and TGF-alpha were used for immunohistochemical detection of each protein in tissue sections of primary tumors from 91 patients who were treated by surgical resection. Levels of immunoreactive EGFR and TGF-alpha were quantified by use of a computerized image analysis system and were normalized to appropriate standards. The logrank test and proportional hazards regression analysis were used to calculate the probability that EGFR and TGF-alpha levels were associated with disease-free survival (i.e., no recurrence of cancer) and cause-specific survival (i.e., patients do not die of their disease). All P values were two-sided.


RESULTS
When tumor levels of EGFR or TGF-alpha were analyzed as continuous variables, disease-free survival and cause-specific survival were reduced among patients with higher levels of EGFR (both P = .0001) or TGF-alpha (both P = .0001). In a multivariate analysis, tumor site, tumor level of EGFR, and tumor level of TGF-alpha were statistically significant predictors of disease-free survival; in a similar analysis, regional lymph node stage and tumor levels of EGFR and of TGF-alpha were significant predictors of cause-specific survival.


CONCLUSIONS
Quantitation of EGFR and TGF-alpha protein levels in primary head and neck squamous cell carcinomas may be useful in identifying subgroups of patients at high risk of tumor recurrence and in guiding therapy.
Rubin Grandis
J
J
Department of Otolaryngology, University of Pittsburgh School of Medicine, and University of Pittsburgh Cancer Institute, PA, USA. jgrandis@vms.cis.pitt.edu
Melhem
M F
MF
Gooding
W E
WE
Day
R
R
Holst
V A
VA
Wagener
M M
MM
Drenning
S D
SD
Tweardy
D J
DJ
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000096:biosynthesis / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000401:mortality / Q000628:therapy; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000032:analysis* / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D015993:Life Tables; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis*; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis; D016211:Transforming Growth Factor alpha / Q000032:analysis* / Q000096:biosynthesis / Q000276:immunology
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors