EXPRESSION OF P53 PROTEIN AND RESISTANCE TO PREOPERATIVE CHEMOTHERAPYIN LOCALLY ADVANCED GASTRIC-CARCINOMA

BACKGROUND. Inactivation of the p53 gene has been reported to be assoc iated with resistance to chemotherapy. The authors evaluated the signi ficance of p53 status to the clinical outcomes of patients with locall y advanced, unresectable gastric carcinoma (LAGC) who received chemoth erapy. METHODS, Thirty chemotherapy-naive patients with LAGC received weekly administration of cisplatin 40 mg/m(2), epi-doxorubicin 35 mg/m (2), 5-fluorouracil 500 mg/m(2), 6S-leucovorin 250 mg/m(2), and glutat hione 1500 mg/m(2). After eight administrations of these agents, patie nts were assessed for response. Biopsy specimens of primary tumors wer e analyzed for p53 status using monoclonal antibody Bp53-12. RESULTS. Characteristics of patients were as follows: The median age was 66 yea rs (range, 44-70 years); 18 were males and 12 were females. Eastern Co operative Oncology Group performance status was 0 for 14 patients and 1 for 16. Histology was intestinal for 13 patients; for 17, it was dif fuse. The site of the primary tumor was the cardia in 8 patients, the body of the stomach in 13, and the antrum in 9. The response rate (ass essed with CT scan and endoscopy) for patients with p53 negative tumor s was significantly higher than for those with overexpression of p53 ( 71% vs. 12%, P = 0.004). CONCLUSIONS, p53 status analyzed before chemo therapy seems to be associated with response to treatment in patients with LAGC. This may provide a useful guide to selecting neoadjuvant ch emotherapy for these patients. Cancer 1998;83: 1917-22, (C) 1998 Ameri can Cancer Society.