Implications of p53 alterations and anti-p53 antibody response in head and neck squamous cell carcinomas.
Point mutations at the tumour suppressor gene p53 are one of the most frequent genetic alterations in squamous cell carcinoma of the head and neck (SCCHN), which lead to the nuclear accumulation and overexpression of inactive p53 protein. The overexpression of mutant p53 protein can induce a specific humoral response in cancer patients. p53 protein was studied in 112 SCCHN. Biopsies and sera samples were collected before initiation of treatment. 74 patients received neoadjuvant chemotherapy (5-fluorouracil-cisplatin-folinic acid). p53 protein expression was evaluated by immunohistochemistry (IHC) on paraffin-embedded sections. The analysis of mutations was assessed by PCR-SSCP of exons 5-10 on DNA from 28 representative cases. Antibodies specific for p53 protein were analysed in sera of 74 patients by an ELISA procedure. Overexpression (> 20% positive cells) of p53 protein was frequent (56%: 63/112) and was correlated with localisation of the primary tumour and tumour stage. p53 mutations were detected in 57% (16/28) of studied cases. The prevalence of p53 antibodies in sera was high (44% 32/74) and among this population, 68% (20/29) had a positive immunophenotype and 67% (6/9) a p53 mutation in the tumour. In addition, the presence of anti-p53 antibodies was slightly associated with complete response to neoadjuvant chemotherapy. If the humoral response seems to be an indicator of the p53 protein status, the detection of anti-p53 antibodies could be a good approach in the early detection of the presence of p53 alterations in SCCHN and recurrent tumours or the appearance of second primary cancer.
Airways Cancer Research Group, Albert Bonniot Institute, La Tronche, France.
J P
JP
Lavieille
C
C
Righini
E
E
Reyt
C
C
Brambilla
C
C
Riva
D000328:Adult; D000368:Aged; D000912:Antibodies, Neoplasm / Q000097:blood*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000276:immunology* / Q000378:metabolism
D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53