Harpole D H, Moore M B, Herndon J E, Aloia T, D'Amico T A, Sporn T, Parr A, Linoila I, Allegra C
Thoracic Oncology Program, Duke University Medical Center, Durham, North Carolina 27710, USA.
Clin Cancer Res. 2001 Mar;7(3):562-9.
The purpose of this study was to define the prognostic value of a group of molecular tumor markers in a well-staged population of patients treated with trimodality therapy for esophageal cancer. The original pretreatment paraffin-embedded endoscopic esophageal tumor biopsy material was obtained from 118 patients treated with concurrent cisplatin + 5-fluorouracil (5-FU) + 45 Gy radiation followed by resection from 1986 until 1997 at the Duke University Comprehensive Cancer Center. Three markers of possible platinum chemotherapy association [metallothionein (MT), glutathione S-transferase-pi (GST-pi), P-glycoprotein (P-gp or multidrug resistance)] and one marker of possible 5-FU association [thymidylate synthase (TS)] were measured using immunohistochemistry. The median cancer-free survival was 25.0 months, with a significantly improved survival for the 38 patients who had a complete response (P < 0.001). High-level expression of GST-pi, P-gp, and TS were associated with a decreased survival. MT was not significant in this population. Multivariate analysis identified high-level expression in two of the platinum markers (GST-pi and P-gp) and the 5-FU marker TS as independent predictors of early recurrence and death. In conclusion, this investigation measured three possible markers associated with platinum and one possible marker associated with 5-FU in a cohort of esophageal cancer patients. Independent prognostic significance was observed, which suggests that it may be possible to predict which patients may benefit most from trimodality therapy. These data need to be reproduced in a prospective investigation.
本研究的目的是确定一组分子肿瘤标志物在接受三联疗法治疗的食管癌患者分期良好人群中的预后价值。原始的治疗前石蜡包埋的食管肿瘤内镜活检材料取自1986年至1997年在杜克大学综合癌症中心接受顺铂+5-氟尿嘧啶（5-FU）+45 Gy放疗并随后进行切除治疗的118例患者。使用免疫组织化学方法检测了三种可能与铂类化疗相关的标志物[金属硫蛋白（MT）、谷胱甘肽S-转移酶-π（GST-π）、P-糖蛋白（P-gp或多药耐药）]和一种可能与5-FU相关的标志物[胸苷酸合成酶（TS）]。无癌生存期中位数为25.0个月，38例完全缓解的患者生存率显著提高（P < 0.001）。GST-π、P-gp和TS的高水平表达与生存率降低相关。MT在该人群中无显著意义。多变量分析确定铂类标志物（GST-π和P-gp）中的两种以及5-FU标志物TS的高水平表达是早期复发和死亡的独立预测因素。总之，本研究在一组食管癌患者中检测了三种可能与铂类相关的标志物和一种可能与5-FU相关的标志物。观察到了独立的预后意义，这表明有可能预测哪些患者可能从三联疗法中获益最多。这些数据需要在前瞻性研究中重现。
