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Expression of multidrug resistance-associated protein1,P-glycoprotein, and thymidylate synthase in gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection.

Authors
Choi, JH; Lim, HY; Joo, HJ; Kim, HS; Yi, JW; Kim, HC; Cho, YK; Kim, MW; Lee, KB
Citation
British journal of cancer, 86(10):1578-1585, 2002
Journal Title
British journal of cancer
ISSN
0007-09201532-1827
Abstract
Both 5-fluorouracil and doxorubicin are commonly used agents in chemotherapy of gastric cancer in adjuvant setting as well as metastatic disease. In a variety of malignancies, high expression of multidrug resistance-associated protein1 and P-glycoprotein has been associated with resistance to doxorubicin, whereas 5-fluorouracil resistance has correlated with the level of thymidylate synthase expression. We evaluated the expression of multidrug resistance-associated protein1, P-glycoprotein, and thymidylate synthase using immunohistochemistry in 103 locally advanced gastric cancer patients (stage IB-IV) who underwent 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection and investigated the association between their expression and clinicopathologic characteristics including prognosis of the patients. While high expression (> or =5% of tumour cells positive) of multidrug resistance-associated protein1 and P-glycoprotein was observed in 70 patients (68%) and 42 patients (41%), respectively, 65 patients (63%) had primary tumours with high expression (> or =25% of tumour cells positive) of thymidylate synthase. There was a significant association between multidrug resistance-associated protein1 and P-glycoprotein expression (P<0.0001) as well as P-glycoprotein and thymidylate synthase expression (P<0.0001). High multidrug resistance-associated protein1 and P-glycoprotein expressions were associated with well and moderately differentiated histology (P<0.0001 and P=0.03, respectively) and intestinal type (P<0.0001 and P=0.009, respectively). High multidrug resistance-associated protein1 expression correlated with lymph node metastasis (P=0.037), advanced stage (P=0.015), and older age (P=0.021). Five-year disease-free survival and overall survival of total patients were 55.2% and 56.2%, respectively, with a median follow-up of 68 months. There were no significant differences in disease-free survival and overall survival according to the expression of multidrug resistance-associated protein1 (P=0.902 and P=0.975, respectively), P-glycoprotein (P=0.987 and P=0.955, respectively), and thymidylate synthase (P=0.604 and P=0.802, respectively). Concurrent high expression of these proteins (high multidrug resistance-associated protein1/P-glycoprotein, high multidrug resistance-associated protein1/thymidylate synthase, high P-glycoprotein/thymidylate synthase) did not correlate with disease-free survival or overall survival. Even high expression of all three proteins was not associated with poor disease-free survival (P=0.919) and overall survival (P=0.852). In conclusion, high expression of multidrug resistance-associated protein1, P-glycoprotein, and thymidylate synthase did not predict poor prognosis of gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy. A larger study including patients treated with surgical resection alone would be necessary.
MeSH terms
Adenocarcinoma/*chemistry/drug therapy/mortality/surgery/therapyAgedAntineoplastic Combined Chemotherapy Protocols/*therapeutic useChemotherapy, AdjuvantCombined Modality TherapyDisease-Free SurvivalDoxorubicin/administration & dosage*Drug Resistance, Multiple*Drug Resistance, NeoplasmFemaleFluorouracil/administration & dosage*GastrectomyHumansImmunotherapyLentinan/administration & dosageLife TablesMaleMiddle AgedMitomycin/administration & dosageNeoplasm Proteins/*analysisP-Glycoprotein/*analysisPicibanil/administration & dosageStomach Neoplasms/*chemistry/drug therapy/mortality/surgery/therapySurvival AnalysisThymidylate Synthase/*analysis
DOI
10.1038/sj.bjc.6600305
PMID
12085207
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Hematology-Oncology
Journal Papers > School of Medicine / Graduate School of Medicine > Pathology
Journal Papers > School of Medicine / Graduate School of Medicine > Surgery
AJOU Authors
최, 진혁임, 호영주, 희재김, 효철조, 용관김, 명욱이, 기범
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