BIOLOGICAL MARKERS AS A PREDICTOR FOR RESPONSE AND PROGNOSIS OF UNRESECTABLE GASTRIC-CANCER PATIENTS TREATED WITH 5-FLUOROURACIL AND CISPLATINUM

We investigated the utility of examining biological markers to predict chemoresponse and survival. The subjects consisted of 39 unresectable gastric cancer patients treated with a combination of 5-fluorouracil and cis-platinum, The expression of p53, bcl-2, thymidylate synthase ( TS), glutathione S-transferase pi (GST-pi), and vascular endothelial g rowth factor (VEGF) in the formalin-fixed biopsy samples of primary tu mors before chemotherapy was examined immunohistochemically. The posit ive rate for VEGF, bcl-2, TS, p53, and GST-pi was 51, 10, 46, 38, and 69%, respectively. VEGF-positive cases showed a higher response rate t han did negative cases (11 of 20 versus 2 of 19 cases; P = 0.0057), Th e cases that were negative for p53, TS, bcl-2, and GST-pi were more li kely to respond to chemotherapy than the cases that were positive for these markers. The 10 cases having 4 or 5 favorable phenotypes (VEGF p ositive, p53 negative, bcl-2 negative, TS negative, and GST-pi negativ e) survived longer than the remaining 29 cases (P = 0.0069). Multivari ate analysis revealed that the number of favorable phenotypes (greater than or equal to 4 versus less than or equal to 3) had a greater impa ct on survival than performance status (0 versus 1 or 2), age (>60 yea rs versus less than or equal to 60 years), macroscopic type (scirrhous versus nonscirrhous), histological type (intestinal versus diffuse), or tumor extent (locally advanced versus metastatic), Immunohistochemi cal examination of biological markers in biopsy samples may be useful in predicting the clinical outcome of unresectable gastric cancer pati ents treated with 5-fluorouracil and cis-platinum.