Document Detail

Immunohistochemical study of c-fos-positive lymphocytes infiltrated into human squamous cell carcinomas of the head and neck during radiation therapy and its clinical significance.
MedLine Citation:
PMID:  9815628     Owner:  NLM     Status:  MEDLINE    
C-fos has been reported to be one of the immediate early genes in signal transduction systems after many kinds of stresses, including ionizing radiation. Changes in c-fos expression induced by radiation therapy in tumor tissues have not yet been reported. In this study, we have attempted to determine whether c-fos expression is induced by radiotherapy in human squamous cell carcinomas of the head and neck and to establish a possible correlation between c-fos expression and the therapeutic effects of radiation therapy. Twenty-seven patients with tumors of the oral cavity, oropharynx, and maxillary sinus were examined, all of which were confirmed as squamous cell carcinomas. After obtaining the patients' informed consent, biopsies were performed before treatment and at doses of 4, 10, and 20 Gy of radiotherapy, and the specimens were preserved in liquid nitrogen for further examination. Serial sectioning of 6 micrometer was performed using a cryostat, and samples were immunohistochemically stained using the streptoavidin-biotin peroxidase method and a monoclonal antibody against c-fos. Three of the 27 patients with squamous cell carcinoma showed slight expression of c-fos in their tumor cells before and/or at 4 or 10 Gy of radiotherapy. The tumors showed high radiosensitivity. Concerning tumor-infiltrating lymphocytes, the rate of moderate or remarkable grades of c-fos-positive lymphocytes before radiotherapy and at radiation doses of 4, 10, and 20 Gy was 8.0, 29.2, 4.8, and 0%, respectively. The relationship between the immunohistochemical findings and the antitumor effect at a radiation dose of 20 Gy was examined on the corresponding H&E-stained sections. In patients whose infiltration of c-fos-positive lymphocytes into tumor tissues were moderate or remarkable at 4 Gy of radiotherapy, the tumors responded significantly well to radiation therapy (P < 0.025, chi2 test), and the patients took a significantly favorable clinical course (P < 0.05, chi2 test). In a sample from one of the patients, c-fos-positive lymphocytes were identified as CD4 positive and CD8 negative. Therefore, the high radiosensitivity of squamous cell carcinomas in our samples could be explained by an overexpression of c-fos in the tumor-infiltrating lymphocytes induced by small doses of radiation therapy, and these activated lymphocytes exerted a cytotoxic effect against the cancer cells.
Y Ogawa; A Nishioka; N Hamada; M Terashima; T Inomata; S Yoshida; H Seguchi; S Kishimoto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  3     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  1997 Dec 
Date Detail:
Created Date:  1999-03-03     Completed Date:  1999-03-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2301-7     Citation Subset:  IM    
Departments of Radiology, Cell Biology, and Otorhinolaryngology, Kochi Medical School, Kochi 783, Japan.
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MeSH Terms
Antigens, CD4 / analysis
Antigens, CD8 / analysis
Carcinoma, Squamous Cell / genetics,  mortality,  pathology*,  radiotherapy*
Disease-Free Survival
Genes, fos*
Head and Neck Neoplasms / genetics,  mortality,  pathology*,  radiotherapy*
Lymphocytes, Tumor-Infiltrating / pathology*
Middle Aged
Neoplasm Staging
Predictive Value of Tests
Proto-Oncogene Proteins c-fos / analysis*
Survival Rate
Time Factors
Reg. No./Substance:
0/Antigens, CD4; 0/Antigens, CD8; 0/Proto-Oncogene Proteins c-fos

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