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Implications of p53 alterations and anti-p53 antibody response in head and neck squamous cell carcinomas
J P Lavieille1, C Righini, E Reyt
1Airways Cancer Research Group, Albert Bonniot Institute, La Tronche, France.
Abstract:
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.
Insights
Mutations in the tumor suppressor gene p53 are common in head and neck cancers. Detecting anti-p53 antibodies in patient sera may aid in early detection of p53 alterations and recurrent tumors.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Point mutations in the p53 tumor suppressor gene are frequent in squamous cell carcinoma of the head and neck (SCCHN).
- These mutations often lead to nuclear accumulation and overexpression of inactive p53 protein.
- Overexpressed mutant p53 protein can elicit a specific humoral immune response in cancer patients.
Purpose of the Study:
- To investigate the prevalence of p53 protein overexpression and mutations in SCCHN.
- To assess the presence of anti-p53 antibodies in SCCHN patients' sera.
- To explore the association between p53 alterations, humoral response, and treatment response.
Main Methods:
- Immunohistochemistry (IHC) for p53 protein expression on 112 SCCHN biopsies.
- PCR-SSCP analysis of p53 gene mutations (exons 5-10) in 28 tumor samples.
- ELISA for detecting anti-p53 antibodies in sera from 74 patients.
Main Results:
- p53 protein overexpression was observed in 56% of SCCHN cases, correlating with tumor location and stage.
- p53 mutations were detected in 57% of the analyzed tumor samples.
- A high prevalence of anti-p53 antibodies (44%) was found in patient sera, with a significant association with p53 mutations and overexpression.
Conclusions:
- The humoral response, indicated by anti-p53 antibodies, appears to reflect the p53 protein status in SCCHN.
- Detection of anti-p53 antibodies may serve as a valuable tool for early detection of p53 alterations.
- This approach could also aid in identifying recurrent tumors or the development of second primary cancers.