Fukuda Hiroyuki, Takiguchi Nobuhiro, Koda Kenji, Oda Kenji, Seike Kazuhiro, Miyazaki Masaru
Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Cancer Invest. 2006 Apr-May;24(3):235-41. doi: 10.1080/07357900600632082.
Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and vascular endothelial growth factor (VEGF) are associated with the effect of 5-fluorouracil (5-FU) based adjuvant chemotherapy. However, very few studies have investigated the relationship between these factors and 5-FU neoadjuvant chemotherapy for primary gastric cancer patients. In this study, we studied the correlation between these markers and the histological chemotherapeutic effect in advanced gastric cancer with neoadjuvant chemotherapy.
Sixty-two primary advanced gastric cancer patients were recruited into the study. One cycle of continuous infusion of 5-FU (300 mg/m2/day, 14 days) plus drip infusion of cisplatin (15 mg/m2/day, Day one and Day two) was performed as neoadjuvant chemotherapy. Histological chemotherapeutic responses of the resected specimens were classified into responders and nonresponders. TS, DPD, VEGF expressions both before and after neoadjuvant chemotherapy were examined immunohistochemically.
There was an association between the TS-low group and the responders (p < 0.05); the DPD-low group and the responders in both biopsy and surgical specimens (p < 0.01). A combination of the low-TS and low-DPD group was further associated with responders (p < 0.01). The immunoexpressions of biopsied and surgical specimens were significantly associated with each other.
Neoadjuvant chemotherapy for primary gastric cancer with one cycle of 5-FU and cisplatin was associated with histological findings in patients with low baseline TS and DPD. This dual determination may predict for efficacy of neoadjuvant treatment with these drugs.
胸苷酸合成酶(TS)、二氢嘧啶脱氢酶(DPD)和血管内皮生长因子(VEGF)与基于5-氟尿嘧啶(5-FU)的辅助化疗效果相关。然而,很少有研究调查这些因素与原发性胃癌患者5-FU新辅助化疗之间的关系。在本研究中,我们研究了这些标志物与新辅助化疗的晚期胃癌组织学化疗效果之间的相关性。
62例原发性晚期胃癌患者纳入研究。进行一个周期的5-FU持续输注(300mg/m²/天,共14天)加顺铂滴注(15mg/m²/天,第1天和第2天)作为新辅助化疗。切除标本的组织学化疗反应分为反应者和无反应者。通过免疫组织化学检查新辅助化疗前后TS、DPD、VEGF的表达情况。
TS低表达组与反应者之间存在关联(p<0.05);DPD低表达组与活检和手术标本中的反应者均相关(p<0.01)。低TS和低DPD组的联合与反应者进一步相关(p<0.01)。活检标本和手术标本的免疫表达彼此显著相关。
对于基线TS和DPD较低的患者,采用一个周期5-FU和顺铂的原发性胃癌新辅助化疗与组织学结果相关。这种双重测定可能预测这些药物新辅助治疗的疗效。