新辅助化疗对胃癌微卫星不稳定性的影响

Influence of Neoadjuvant Chemotherapy on Microsatellite Instability in Gastric Carcinoma

背景与目的:多数胃癌新辅助化疗的临床试验结果是肯定的,而微卫星不稳定性(microsatelliteinstability,MSI)已被认为是细胞癌变的新机理。本文拟探讨新辅助化疗对胃癌MSI的影响。方法:选取D2S123、D3S1298两个微卫星位点,从48例已行氟尿嘧啶/醛氢叶酸(5-FU/CF)术前化疗胃癌患者的石蜡标本中提取DNA,经PCR扩增、变性聚丙烯酰胺凝胶电泳、银盐染色,采用自身对照的方法,比较化疗前后胃癌组织MSI的表现;采用!2检验分析新辅助化疗对胃癌MSI的影响。结果:术前标本两个位点共检出MSI阳性15例,检出率31.3%。术后标本检出MSI阳性6例,检出率为12.5%。共有9例样本由化疗前的MSI阳性变为MSI阴性,无MSI阴性转为MSI阳性的病例。经!2检验,化疗前后的MSI阳性率有显著性差异(31.3%vs.12.5%,P=0.026)。结论:5-FU/CF新辅助化疗方案对胃癌MSI有影响。新辅助化疗后,部分MSI阳性的病例可以表现为阴性,但对MSI阴性病例无影响。

BACKGROUND ＆ OBJECTIVE： Most results from clinical trials of neoadjuvant chemotherapy for gastric carcinoma are certain. Meanwhile, microsatellite instability （MSI） is thought to be a new mechanism of cell canceration. This study was to investigate the influence of neoadjuvant chemotherapy on MSI in gastric carcinoma. METHODS： Two microsatellite loci D2S123 and D3S1298 in tumor samples from 48 patients with gastric carcinoma, received preoperative chemotherapy of 5-fluorouracil （5-FU） and leucovorin （CF）, were analyzed by polymerase chain reaction （PCR）, electrophoresis on 8% denatured polyacrylamide gel, and silver staining. The microsatellite statuses of preoperative and postoperative specimens were compared. Chi-square test was used to analyze the influence of neoadjuvant chemotherapy on MSI in gastric carcinoma. RESULTS： The detection rate of MSI was significantly higher in preoperative samples than in postoperative samples （31.3% vs. 12.5%, P=0.026）. After neoadjuvant chemotherapy, 9 cases changed from MSI-positive to MSI-negative, while no MSI-negative cases became MSI-positive. CONCLUSION： The neoadjuvant chemotherapy regimen of 5-FU/CF can induce some MSI-positive gastric carcinoma change to MSI- negative, but has no effect on MSI-negative cases.