p53 Gene status in relation to ex vivo chemosensitivity of non-small cell lung cancer.
OBJECTIVE
About 40% of non-small cell lung cancer (NSCLC) patients are candidates for systemic chemotherapy, despite the fact that at diagnosis most NSCLC are usually chemoresistant both in vivo and ex vivo. It is important to develop sufficient methods of prediction of the response to chemotherapy and to find molecular markers that may prognose this response. Therefore, a study on the relationship of p53gene status to the ex vivo chemosensitivity of primary human NSCLC was performed.


METHODS
Three drug combinations (carboplatin/etoposide, cyclophosphamide/etoposide/epirubicin, and paclitaxel/carboplatin) were tested in a modified ATP cell viability assay. A group of 28 cases of primary human NSCLC was assessed.


RESULTS
Ex vivo chemosensitivity testing showed that tumors with p53 mutations were significantly more resistant to the cyclophosphamide/etoposide/epirubicin regimen than with normal p53 gene ( P = 0.012). However, no correlation was observed for two other treatment regimens.


CONCLUSIONS
Mutations in the p53gene can lead to enhanced chemoresistance, confirming the hypothesis that the p53 gene may serve as a marker of tumor response to treatment in NSCLC. However, the data also illustrate that some additional factors might contribute to drug resistance of the examined tumors.
Vogt
U
U
European Laboratory Association Section Ibbenbüren, Roggenkampstrasse 10, 49477 Ibbenbüren, Germany.
Zaczek
A
A
Klinke
F
F
Granetzny
A
A
Bielawski
K
K
Falkiewicz
B
B
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D016190:Carboplatin / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D003520:Cyclophosphamide / Q000494:pharmacology; D004252:DNA Mutational Analysis; D018076:DNA, Complementary; D004273:DNA, Neoplasm / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015251:Epirubicin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D015251:Epirubicin; D005047:Etoposide; D003520:Cyclophosphamide; D016190:Carboplatin