Elevated expression of thymidylate synthase in doxorubicin resistant human non small cell lung carcinomas.
Human non-small cell lung carcinomas of previously untreated patients were analyzed for expression of thymidylate synthase (TS) using immunohistochemistry. Of the 94 tumors, 67 were positive for TS and 27 negative. A significant correlation between the expression of TS and the resistance to doxorubicin was found (p < 0.0001). Eighty-four percent of the TS-positive tumors were resistant to doxorubicin, whereas of the 27 TS-negative tumors only 44 percent were resistant. A group of patients (n = 13) were treated with combination chemotherapy including 5-fluorouracil, doxorubicin and cisplatinum. Seven of the 8 tumors which were TS-positive were clinically progressive, whereas 4 of 5 tumors which were TS-negative showed clinical remission after chemotherapy (p < 0.05; Fisher exact test). The patients whose tumors were TS negative lived significantly longer than those with TS-positive tumors. The median survival times were 185 weeks for patients with TS-negative and 41 weeks for patients with TS-positive tumors (p < 0.05; log-rank-test). Thus the expression of TS is a strong prognostic factor for resistance of tumors, clinical course and survival of patients with non-small cell lung carcinomas.
Volm
M
M
German Cancer Research Center, Heidelberg.
Mattern
J
J
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance / Q000502:physiology*; D004354:Drug Screening Assays, Antitumor; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000378:metabolism*
D014408:Biomarkers, Tumor; D004317:Doxorubicin; D013940:Thymidylate Synthase