진행성 위암 전절제후 5-Fluorouracil로 치료한 환자에서종양내 Thymidylate Synthase 과발현의 예후적 의의
A High Thymidylate Synthase Expression is Related to Better Outcome for Advanced Gastric Cancer Patients Treated with 5-FU Chemotherapy after Curative Resection
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Abstract
Background : The expressions of thymidylate synthase (TS), E2F-1, pRb, and p53 are correlated with DNA synthesis. The significance of their expressions is still controversial for predicting the outcome of 5-fluorouracil (5-FU) therapy in the patients with advanced gastric carcinoma. Furthermore, their prognostic value in the metastatic lesions of gastric carcinoma has not yet been confirmed. Methods : To ascertain their prognostic value, we immunohistochemically analyzed the expressions of TS, E2F-1, pRb, and p53 in the primary tumors and the related metastatic lymph nodes, and we then compared the survival between the high and low expression group of each protein. Ninety four patients with advanced gastric carcinoma who were treated by complete resection and adjuvant 5-FU chemotherapy were analyzed. Results : The TS expression in primary tumors was significantly correlated with that of E2F-1. The expression of these genes showed no significant difference between the primary tumors and the metastatic lymph nodes except for E2F-1, which was significantly higher in the lymph node metastasis than in the primary tumors. After complete resection and 5-FU-based adjuvant chemotherapy, patients with a high TS expression in the primary tumors showed a longer survival than those patients having primary tumors with a low TS expression (p=0.0392). Conclusion : A high TS expression in the primary tumors may be related to a better outcome for advanced gastric cancer patients who were treated with 5-FU chemotherapy after curative resection.
참고문헌 (30)
- Lee HJ, "Gastric cancer in Korea", 5, pp.177~182 (2002)
- Yao JC, "Combined-modality therapyfor gastric cancer", 21, pp.223~227 (2003)
- Danenberg PV, "Thymidylate synthase:a target-enzyme in cancerchemotherapy", 473, pp.73~92 (1977)
- Santi DV, "Mechanism of interaction ofthymidylate synthase with 5-fluorodeoxyuridylate", 13, pp.471~81 (1974)
- Tsujitani S, "Expression of thymidylate synthasein relation to survival and chemosensitivity in gastric cancerpatients", 19, pp.189~195 (2000)
- Formentini A, "Thymidylate synthaseexpression and prognosis of patients with gastrointestinal cancersreceiving adjuvant chemotherapy:a review", 389, pp.405~413 (2004)
- Fidler IJ, "Seed and soil revisited:contribution of the organ microenvironmentto cancer metastasis", 10, pp.257~ (2001)
- Aschele C, "Thymidylatesynthase protein expression in primary colorectal cancer comparedwith the corresponding distant metastases and relationshipwith the clinical response to 5-fluorouracil", 6, pp.4797~4802 (2000)
- Gorlick R, "Higher levels of thymidylatesynthase gene expression are observed in pulmonary as comparedwith hepatic metastases of colorectal adenocarcinoma", 16, pp.1465~1469 (1998)
- Trocha SD, "Differential expression of thymidylate synthase in colorectal tumorsand matched lymph nodes:impact on adjuvant treatment", 69, pp.918~922 (2003)
- Kuniyasu T, "Immunohistochemicalevaluation of thymidylate synthase in gastric carcinoma usinga new polyclonal antibody:the clinical role of thymidylate synthaseas a prognostic indicator and its therapeutic usefulness", 83, pp.1300~1306 (1998)
- Nevins JR, "E2F:a link between the Rb tumor suppressor proteinand viral oncoproteins", 258, pp.424~9 (1992)
- Nevins JR, "Toward an understanding of the functional complexityof the E2F and retinoblastoma families", 9, pp.585~593 (1998)
- Banerjee D, "Role of E2F-1 in chemosensitivity", 58, pp.4292~4296 (1998)
- Banerjee D, "Levels of E2F-1 expressionare higher in lung metastasis of colon cancer as compared with hepaticmetastasis and correlate with levels of thymidylate synthase", 60, pp.2365~2367 (2000)
- Lane DP, "p53,guardian of the genome", 358, pp.15~16 (1992)
- Longley DB, "The role of thymidylate synthaseinduction in modulating p53-regulated gene expression inresponse to 5-fluorouracil and antifolates", 62, pp.2644~2649 (2002)
- Bunz F, "Disruption of p53 in humancancer cells alters the responses to therapeutic agents", 104, pp.263~269 (1999)
- Frederick LG,, "AJCC cancer Staging Manual.6th ed", pp.99~102 (2002), Springer-Verlag
- Kumar B, "Tissue microarrays:apractical guide", 36, pp.295~300 (2004)
- Lauren P, "The two histological main types of gastric carcinoma:diffuse and socalled intestinal type carcinoma. An attempt at a histologicalclassification.", 64, pp.34~
- Longley DB, "Clinical significance ofprognostic and predictive markers in colorectal cancer", 2, pp.209~216 (2002)
- Bates S, "p14ARF links the tumour suppressorsRB and p53", 395, pp.124~125 (1998)
- Broll R, "Influence of thymidylate synthaseand p53 protein expression on clinical outcome in patientswith colorectal cancer", 20, pp.94~102 (2005)
- Min BW, "Significance of thymidylatesynthase expression in colorectal cancer", 62, pp.408~414 (2002)
- Popat S, "Thymidylate synthase expressionand prognosis in colorectal cancer:a systematic review andmeta-analysis", 22, pp.529~536 (2004)
- Midgley R, "Colorectal cancer", 353, pp.391~399 (1999)
- Johnstone PG, "The role of thymidylatesynthase expression in prognosis and outcome of adjuvant chemotherapyin patients with rectal cancer", 12, pp.2640~7 (1994)
- Nam EM, "The relationship between thymidylatesynthase expression and prognosis in gastric adenocarcinoma", 56, pp.339~346 (1999)
- Ishida Y, "Association of thymidylate synthase gene polymorphism withits mRNA and protein expression and with prognosis in gastriccancer", 22, pp.2805~2809 (2002)
