Journal of Clinical Oncology, Vol 15, 1030-1038, Copyright © 1997 by American Society of Clinical Oncology
Markers of radioresistance in squamous cell carcinomas of the head and neck: a clinicopathologic and immunohistochemical study
H Raybaud-Diogene, A Fortin, R Morency, J Roy, RA Monteil and B Tetu
Department of Pathology, Faculte de Medicine, Universite Laval, Quebec, Canada.
PURPOSE: The lack of accurate criteria to predict the response to
radiotherapy for individual patients with squamous cell carcinoma of the
head and neck (HN-SCC) remains a major problem. The purpose of this study
was to investigate the role of several biologic tumor markers to complement
clinical prognostic factors in the assessment of response to radiotherapy
in SCCs. PATIENTS AND METHODS: p53, ki-67, c-erb B-2, heat- shock
protein-27 (HSP-27), and glutathione S transferase (GSTpi) were evaluated
by immunohistochemistry on biopsies from 101 patients treated for head and
neck cancer by radical radiotherapy. Expression of each marker was
correlated with local control and survival using Kaplan- Meier curves. A
Cox regression multivariate analysis was also performed that included all
clinical and immunohistochemical variables. RESULTS: Expression of p53 and
low cell proliferation allowed identification of patients whose tumors did
not respond to radiation. Patients with p53- expressing tumors displayed a
relative risk (RR) of 3.78 for not being controlled by radiotherapy
compared with patients with p53-negative tumors. For tumors with a high
growth fraction (ki-67 > 20%) the RR was 0.25 compared with tumors with
a low growth fraction (ki-67 < 20%). When p53 expression and cell
proliferation were considered simultaneously in a Cox model, the
association with resistance to radiation was significant (P = .000004). The
RR for resistance with one (p53 staining or ki-67 < 20%) or two (p53
staining and ki-67 < 20%) unfavorable markers was, respectively, 3.8 and
14.87. CONCLUSION: Patients whose tumor expressed p53 with low growth
fraction (ki-67 < 20%) had a strong probability not to respond to
radiation therapy. Similarly, absence of p53 expression with a high cell
proliferation predicted an excellent outcome after radiotherapy even for
patients with advanced disease. Prediction of the outcome of radiotherapy
would eventually facilitate the early choice of an adequate treatment.
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