Differential c-myc, c-jun, c-raf and p53 expression in squamous cell carcinoma of the head and neck: implication in drug and radioresistance.
The expression of oncogenes c-myc, c-jun and c-raf and tumour suppressor gene p53 was assessed by northern blot analysis of 42 tumours and p53 protein expression by immunohistochemistry on paraffin-embedded sections from 36 specimens of squamous cell carcinoma of the head and neck (SCCHN) obtained before therapy. Of the 42 tumours, 89, 100 and 100% expressed c-myc, c-jun and c-raf oncogenes, respectively. These oncogene expressions did not correlate with sex, age or clinical stage of the disease. However, an association was found between low c-myc expression (P = 0.0001) and high c-jun expression (P = 0.0001) and absence of tumoral response to neoadjuvant chemotherapy. On the other hand, c-raf overexpression was observed in patients resistant to radiation therapy (P = 0.0494). Forty-two per cent of the tumours showed p53 protein overexpression, which did not correlate with any clinical parameter. This p53 protein overexpression was associated with high p53 mRNA levels (REL) (P = 0.0223). A correlation was found between increased c-myc RNA expression and lack of p53 protein expression (P = 0.0407). In addition, a lack of p53 protein expression was indicative of tumour relapse (P = 0.05). None of these biological parameters were associated with disease-free survival (Cox-Mantel test). In conclusion, the overexpression of c-myc, c-jun and c-raf may be independently associated to tumoral response to chemotherapy or radiotherapy, or to tumour relapse, but fail to predict long-term survival.
Riva
C
C
Lung and Airways Cancer Research Group, Albert Bonniot Institute, La Tronche, France.
Lavieille
J P
JP
Reyt
E
E
Brambilla
E
E
Lunardi
J
J
Brambilla
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015152:Blotting, Northern; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf; D011519:Proto-Oncogenes; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf