The TP53 genotype but not immunohistochemical result is predictive of response to cisplatin-based neoadjuvant therapy in stage III non-small cell lung cancer.
BACKGROUND
The cytotoxic effects of cisplatin and anthracyclins have been attributed to apoptosis induction, which has been recognized as a major function of the TP53 gene. The TP53 gene appears to be mutated in about 50% of cases of non-small cell lung cancer. A possible dependence of chemotherapy response on TP53 genotype was evaluated retrospectively in a group of patients with advanced non-small cell lung cancer and induction treatment.


METHODS
Patients with complete or partial remission were compared with those with stable or progressive disease with respect to TP53 genotype and overall survival. Mutations in the TP53 gene were detected by complete direct sequencing (exons 2-11).


RESULTS
A normal TP53 genotype proved to be significantly associated with major response to chemotherapy (P <.001). Overall, no association was found between p53 protein expression and TP53 genotype. A normal TP53 genotype was found to be highly sensitive in predicting response to treatment, whereas a mutant genotype was revealed to be specific in predicting lack of response. The difference in overall length of survival was significant between patients exhibiting a normal TP53 genotype (corresponding to those whose disease responded to chemotherapy) and patients showing mutant TP53 genotype (corresponding to those who had disease resistant to chemotherapy, P =.027).


CONCLUSIONS
In a small cohort of patients with advanced non-small cell lung cancer we found a direct link between normal TP53 genotype and response to cisplatin-based induction treatment and also between mutant genotype and resistance to treatment, whereas p53 immunohistochemical result was predictive of neither.
Kandioler-Eckersberger
D
D
Departments of Thoracic and Cardiovascular Surgery,Internal Medicine, Medical Computer Sciences, and Clinical Pathology, University of Vienna, Waehringer-Guertel 18-20,A-1090 Vienna, Austria.
Kappel
S
S
Mittlböck
M
M
Dekan
G
G
Ludwig
C
C
Janschek
E
E
Pirker
R
R
Wolner
E
E
Eckersberger
F
F
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D002945:Cisplatin / Q000008:administration & dosage; D016158:Genes, p53 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D009154:Mutation; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D016159:Tumor Suppressor Protein p53; D002945:Cisplatin; D007069:Ifosfamide