Expression of transforming growth factor-alpha, epidermal growth factor receptor and platelet-derived growth factors A and B in oropharyngeal cancers treated by curative radiation therapy.
OBJECTIVE
Epidermal growth factor receptor (EGFR) has been implicated in cellular responses to ionizing radiation and represents a major target for current radiosensitizing strategies. We wished to ascertain whether a correlation existed between the expression of EGFR, transforming growth factor-alpha (TGFalpha) and platelet-derived growth factors A and B (PDGF-A and PDGF-B) and treatment outcome in a group of patients with oropharyngeal cancer who had undergone curative radiation therapy. We also assessed the relationship existing between each of the aforementioned proteins and intratumoral microvessel densities (IMD) which have been previously reported (Int J Radiat Oncol Biol Phys 2000;48:17-25.


METHODS
Pretherapeutic tumor biopsies from 95 patients were immunohistochemically stained and their immunoreactivities evaluated semi-quantitatively. The statistical analyses included Cox regression for calculating risk ratios of survival endpoints and logistic regression for determining odds ratios for the development of distant metastasis.


RESULTS
Local tumor control as well as disease-free and overall survival were independent of protein expression levels, whereas combined TGFalpha and EGFR immunoreactivities were closely related to IMD (P = 0.003). The expression levels of these two proteins were also correlated to each other (P = 0.015). Expression of PDGF-B occurred in 54% of cases and was associated with an increase in the risk of developing distant metastasis (P = 0.011).


CONCLUSIONS
Tumoral levels of TGFalpha, EGFR and PDGF-A/B are not predictive of radioresponsiveness in oropharyngeal cancers. The association between IMD and immunoreactivity for TGFalpha and EGFR indicates the involvement of these proteins in the promotion of angiogenesis in these tumors. PDGF-B should be further evaluated as a prognostic marker for squamous cell cancer of the head and neck.
Aebersold
Daniel M
DM
Department of Radiation Oncology, University of Bern, Inselspital, Bern, Switzerland.
Froehlich
Susanne C
SC
Jonczy
Maciej
M
Beer
Karl T
KT
Laissue
Jean
J
Greiner
Richard H
RH
Djonov
Valentin
V
D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D009959:Oropharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D010982:Platelet-Derived Growth Factor / Q000032:analysis / Q000096:biosynthesis*; D016016:Proportional Hazards Models; D016211:Transforming Growth Factor alpha / Q000032:analysis / Q000096:biosynthesis*
D010982:Platelet-Derived Growth Factor; D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors