Glutathion S transferase pi indicates chemotherapy resistance in breast cancer.
BACKGROUND
Breast cancer is the most common malignant disease of women. Pathologic response of breast cancer to chemotherapy has a great prognostic importance. Glutathion S Transferases (GSTs) might detoxify chemotherapeutic drugs within the cancer cells, thus contributing to chemotherapy resistance. The pi isoenzyme of GSTs seems to be of great relevance. Thus, we hypothesized that GSTpi expression in cancer biopsy can be a prognostic indicator for resistance to chemotherapy. To test this hypothesis, we evaluated before and after chemotherapy, tumor size, apoptosis of tumor cells with TUNEL assay, and proliferation of tumor cells by determining PCNA expression in biopsy samples, or in the surgically removed tumor tissue of GSTpi (-), and GSTpi (+) cases.


METHODS
GSTpi immunoreactivity was determined in 42 female patients with breast cancer. Patients were divided into two groups according to the expression of GSTpi in the pre-treatment biopsy specimen: (+) (n = 22) and (n = 20) samples were analyzed. Surgery was performed 2 weeks after a single intravenous injection of the chemotherapeutic drugs [5-fluorouracil, adriamycin, mitomycin (FAM protocol)].


RESULTS
Pre-chemotherapy values of tumor size, apoptosis, or proliferation did not differ between GSTpi (-) and (+) samples. Chemotherapy significantly inhibited tumor growth, and cell proliferation, and induced apoptosis in GSTpi (-) cases. However, these effects were significantly reduced in GSTpi (+) patients.


CONCLUSIONS
These results suggest, that the presence of GSTpi in breast cancer tissue is a bad prognostic indicator, and these tumors are largely resistant to chemotherapy. Thus, GSTpi might be important in inactivating one or more of the chemotherapeutic agents used in this treatment.
Su
Fengxi
F
Department of Surgery, Sun-Yat-Sen Memorial Hospital, Sun-Yat-Sen University of Medical Science, Guangzhou, People's Republic of China.
Hu
Xiaoqu
X
Jia
Weijuan
W
Gong
Chang
C
Song
Erwei
E
Hamar
Peter
P
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008408:Mastectomy; D008875:Middle Aged; D016685:Mitomycin / Q000627:therapeutic use; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D016896:Treatment Outcome
D007527:Isoenzymes; D016685:Mitomycin; D004317:Doxorubicin; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D005472:Fluorouracil