bcl-2 protein expression correlates with recurrence and survival in early stage head and neck cancer treated by radiotherapy.
Inherent cellular radioresistance plays a critical role in the failure of radiation therapy (RT). The proto-oncogene bcl-2 encodes a protein that inhibits apoptosis, a common mechanism of cell death induced by several genotoxic agents, including gamma-radiation. Thus, it is likely that bcl-2 gene expression could be involved in the complex mechanisms of radioresistance in human tumors with some prognostic implications. In this study, we analyzed the predictive relevance of bcl-2 expression on 5-year disease-free and overall survival in patients with early stage squamous cell carcinoma of the head and neck (SCCHN) primary treated with RT. The expression of bcl-2 was analyzed by immunohistochemistry on paraffin-embedded sections from 71 consecutive stage I-II SCCHN patients treated with curative RT. We detected bcl-2 protein in 21% of SCCHN studied. A suggestive association was observed between tobacco exposure and bcl-2 protein expression (P < 0.1); this association was stronger in those patients who failed primary RT (P = 0.03). Moreover, we documented a higher rate of bcl-2 immunoreactive tumors in postirradiated biopsies from relapsed patients than in preirradiated ones (P = 0.03). In both univariate and multivariate analyses, bcl-2 expression was the most important indicator for disease-free survival (P = 0.08 and P = 0.01, respectively) and overall survival (P = 0.004 and P = 0.05) within 5 years of RT. The present study indicates that the proto-oncogene bcl-2 is abnormally expressed in some SCCHN, and its expression may prove to be a useful tool in selecting patients for conventional RT with clear prognostic implications.
Gallo
O
O
Institute of Otolaryngology Head and Neck Surgery, Institute of Pathology, University of Florence, Viale G. B. Morgagni 85, 1-50134, Florence, Italy.
Boddi
V
V
Calzolari
A
A
Simonetti
L
L
Trovati
M
M
Bianchi
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000401:mortality / Q000532:radiotherapy*; D005260:Female; D006258:Head and Neck Neoplasms / Q000737:chemistry / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000737:chemistry*; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D015996:Survival Rate
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2