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p53 and bcl-2 expression in locally advanced squamous cell head-neck cancer treated with platinum based chemotherapy
A Giatromanolaki1, M Koukourakis, T Zaramboukas
1Department of Radiation and Medical Oncology, University Hospital of Iraklion, Crete, Greece.
Background:
The role of apoptosis regulating oncoproteins in defining response to cytotoxic therapy remains poorly understood. Loss of wild type p53 function and bcl-2 protein overexpression are well known to inhibit the apoptotic pathway in in vitro studies.
Methods:
We immunohistochemically examined the nuclear accumulation of mutant p53 and the cytoplasmic overexpression of bcl-2 proteins in 76 patients with locally advanced inoperable squamous cell cancer of the head and neck area. Patients were treated with platinum based chemotherapy and radiotherapy (37 with induction and 39 with concurrent chemotherapy). The median follow up period was 72 months.
Results:
Thirty five (46%) cases were positive for p53 and 41 (54%) negative, whilst 19 (25%) and 57 (75%) cases were positive and negative for bcl-2 respectively. A high percentage of bcl-2 positive cells was associated with a low incidence of nodal involvement. A statistically significant higher percentage of p53 positive cells was observed in the group of patients with complete disappearance of the disease as compared to the group with residual disease after treatment (p = 0.01). High percentage of p53 positive cells and concurrent chemoradiotherapy was associated with better local progression free survival (p = 0.05 and 0.02). In multivariate analysis, the type of chemotherapy (concurrent vs. induction) was the only significant prognostic variable for local relapse (p = 0.02) and overall survival (p = 0.03).
Conclusions:
The present study provides evidence that p53 nuclear accumulation may be associated with better response to DNA damaging cytotoxic agents. The association of wild type p53 loss with decreased DNA repair enzyme activity is a possible explanation. Induction platinum based chemotherapy may contribute to the selection of clonogenic cells with a radioresistant phenotype.
Insights
p53 nuclear accumulation may predict a better response to chemotherapy and radiotherapy in head and neck cancer patients. Concurrent chemoradiotherapy improved survival, while induction chemotherapy may select for radioresistant cells.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The role of apoptosis-regulating oncoproteins in predicting treatment response is unclear.
- Wild type p53 loss and bcl-2 overexpression are known to inhibit apoptosis in vitro.
Purpose of the Study:
- To investigate the association between p53 and bcl-2 protein expression and treatment outcomes in head and neck cancer.
- To evaluate the impact of chemotherapy and radiotherapy on survival and disease progression.
Main Methods:
- Immunohistochemical analysis of p53 and bcl-2 in 76 head and neck cancer patients.
- Patients received platinum-based chemotherapy and radiotherapy (induction or concurrent).
- Median follow-up was 72 months.
Main Results:
- 46% of cases were positive for p53, 25% for bcl-2.
- High p53 expression correlated with complete disease disappearance and better progression-free survival with concurrent chemoradiotherapy.
- Concurrent chemotherapy was the only significant prognostic variable for local relapse and overall survival.
Conclusions:
- p53 nuclear accumulation may indicate a better response to DNA-damaging agents.
- Wild type p53 loss might be linked to reduced DNA repair activity.
- Induction chemotherapy could select for radioresistant cancer cells.