Allelic Imbalance at p53 and Microsatellite Instability Are Predictive Markers for Resistance to Chemotherapy in Gastric Carcinoma
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Combined treatment with 5-fluorouracil and cisplatin (FP chemotherapy) is an effective neoadjuvant regimen for gastric carcinoma. However, it is ineffective in half of all patients. This study tests the hypothesis that genetic markers might identify those patients with gastric cancer who would respond to neoadjuvant FP chemotherapy.
Materials and Methods
A total of 23 patients with gastric carcinoma were treated with neoadjuvant chemotherapy. Pretreatment biopsy specimens before neoadjuvant chemotherapy were obtained from 15 of 23 patients, and resected tumors were obtained from all 23. Genetic studies were performed to detect allelic imbalance (AI), microsatellite instability (MSI), and K-ras mutation.
A clinical response was observed in 13 of 23 patients. Kaplan–Meier survival curve showed that clinical responder group had a significantly higher likelihood of overall survival (P = 0.0165), compared with nonresponder group. In 23 resection specimens, 10 of 23 tumors presented AI at the p53 locus and/or MSI; 8 of the 10 tumors were nonresponders, while 12 of 13 tumors without p53 AI or MSI were responders (P = 0.0007). In 15 pretreatment biopsy specimens, 8 tumors had p53 AI and/or MSI; 7 of the 8 tumors were nonresponders, while 6 of 7 tumors without p53 AI or MSI were responders to preoperative chemotherapy (P = 0.008). Tumors with AI at the p53 locus and/or MSI were significantly more resistant to neoadjuvant chemotherapy. No relationship was found between K-ras mutations and responses.
Analysis for p53 AI and MSI might represent a clinically useful approach to predicting the response to neoadjuvant FP chemotherapy in gastric carcinoma.
KeywordsGastric Cancer Gastric Carcinoma Preoperative Chemotherapy Allelic Imbalance Pretreatment Biopsy Specimen
This study is partially founded by Grants in Aid for Scientific Research (No. 18591475, 20591073, and 18390369) from the Ministry of Education, Science, Sports, Culture, and Technology of Japan, by a JSGE Grant in Aid for Scientific Research, by a Grant in Aid for Kobayashi Foundation for Innovative Cancer Chemotherapy, by a Grant in Aid for the Sagawa Foundation for Cancer Research, by a Grant in Aid for the Osaka Medical Research Foundation for Incurable Diseases, and by NIH grant R01 CA75821 to CRB. The authors have no conflicts of interest to disclose.
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