Cumulative prognostic value of p53 mutations and bcl-2 protein expression in head-and-neck cancer treated by radiotherapy.
We investigated the prognostic significance of p53-gene mutation (exon 5-9) and bcl-2-protein expression in primary squamous-cell carcinoma of the head and neck (HNSCC) treated by curative radiotherapy (RT). Primary squamous-cell carcinomas for analysis were obtained from 85 consecutive head-and-neck-cancer patients, with complete follow-up data. We detected bcl-2 protein in 24% (20/85) of HNSCC studied; 38 (45%) of the 85 tumours had cells bearing p53 mutations. A strong association was observed between tobacco exposure and bcl-2-protein expression (p = 0.003), an association also evident in those patients who had a p53-mutated carcinoma (p = 0.049). Moreover, we found that most of the bcl-2-positive cancers (70%) were also mutated in the p53 gene (p = 0.010). In univariate and in multivariate analyses, the simultaneous detection of bcl-2 expression and a p53-gene mutation in a tumour biopsy specimen was associated with greater risk of locoregional failure (p = 0.002 and 0.001 respectively) and worse survival (p = 0. 045 and 0.033) within 5 years in HNSCC patients treated by RT. The present study shows a cumulative prognostic value of simultaneous detection of bcl-2 over-expression and p53-gene aberration in some primary HNSCC treated with conventional RT, and provides further evidence for cross-talk between p53 and bcl-2, suggesting that these genes are important determinants of radiation-induced apoptosis, thereby modulating resistance to RT. Int. J. Cancer (Pred. Oncol.) 84:573-579, 1999.
Gallo
O
O
Institute of Otolaryngology, Head and Neck Surgery, University of Florence, Italy. o.gallo@dfc.unifi.it
Chiarelli
I
I
Boddi
V
V
Bocciolini
C
C
Bruschini
L
L
Porfirio
B
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics* / Q000532:radiotherapy; D018572:Disease-Free Survival; D005260:Female; D019254:Genes, bcl-2 / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000532:radiotherapy; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015996:Survival Rate; D013997:Time Factors
D019253:Proto-Oncogene Proteins c-bcl-2