p53 mutation, but not in vitro predictor genes of therapeutic efficacy of cisplatin, is clinically relevant in comparing partial and complete responder cases of maxillary squamous cell carcinoma.
To predict the efficacy of cisplatin and radiation therapy for maxillary squamous cell carcinoma, we examined the mRNA expression of 14 cisplatin-resistant genes and p53 mutation in specimens biopsied from patients prior to initiation of therapy. Five of 10 patients had mutations in the p53 gene, of whom four had residual tumors pathologically following chemoradiotherapy (p=0.0476). Of 14 genes examined, the mRNA expression of ATP7B was significantly lower in cases that were resistant to chemoradiotherapy. Six genes including multidrug resistance protein 1 (MDR-1), multidrug resistance associated protein 1 (MRP-1), Cu++ transporting, beta polypeptide (ATP7B), xeroderma pigmentosum, complementation group A (XPA), excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC-1) and B-cell CLL/lymphoma 2 (BCL2) were down-regulated in cases of recurrent cancers. These results show that the evaluation of p53 mutation provides the most useful predictor of therapeutic effects. In responder cases, the drug-resistant genes that were determined in cell lines by culture do not necessarily translate into clinical relevance.
Kudo
Itsuhiro
I
Department of Otorhinolaryngology-Head and Neck Surgery, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan.
Esumi
Mariko
M
Kida
Akihiro
A
Ikeda
Minoru
M
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008441:Maxillary Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D002945:Cisplatin