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P53 mutation correlates with cisplatin sensitivity in head and neck squamous cell carcinoma lines
Carol R Bradford1, Shaobo Zhu, Haruko Ogawa
1Department of Otolaryngology-Head and Neck Surgery, 1904 Taubman Center, University of Michigan, Ann Arbor, Michigan 48109-0312, USA. cbradford@umich.edu
Background:
A critical factor for successful organ preservation treatment in head and neck cancer may be selecting tumors that respond to chemotherapy and radiation. Previous results in patients indicated that tumors that overexpressed p53 were more sensitive to chemotherapy than those that did not overexpress p53.
Methods:
To determine the relationship of p53 mutations to sensitivity to cisplatin in vitro, 23 head and neck squamous cell carcinoma (HNSCC) cell lines were analyzed for cisplatin sensitivity, p53 expression, and p53 mutation status.
Results:
Mutations of the p53 gene were identified in 13 of 23 of the cell lines tested. Mutation of the p53 gene was significantly associated with high levels of expression of the p53 protein. The average ID(50) (drug dose required to inhibit 50% of cell growth) for cell lines with mutant p53 was 6.8 microM, whereas the average ID(50) for cell lines with wild-type p53 was 13.7 microM.
Conclusions:
These in vitro data support a role for mutation of the p53 tumor suppressor gene as a marker for response to cisplatin in HNSCC.