P53 mutation correlates with cisplatin sensitivity in head and neck squamous cell carcinoma lines.
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.
Bradford
Carol R
CR
Department of Otolaryngology-Head and Neck Surgery, 1904 Taubman Center, University of Michigan, Ann Arbor, Michigan 48109-0312, USA. cbradford@umich.edu
Zhu
Shaobo
S
Ogawa
Haruko
H
Ogawa
Tetsuya
T
Ubell
Matthew
M
Narayan
Ajita
A
Johnson
Garfield
G
Wolf
Gregory T
GT
Fisher
Susan G
SG
Carey
Thomas E
TE
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005091:Exons; D015870:Gene Expression / Q000187:drug effects; D016158:Genes, p53; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009154:Mutation; D014407:Tumor Cells, Cultured / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin