Sulzyc-Bielicka Violetta, Domagala Pawel, Bielicki Dariusz, Safranow Krzysztof, Domagala Wenancjusz
Department of Clinical Oncology, Pomeranian Medical University, Szczecin, Poland.
Cell Oncol (Dordr). 2014 Feb;37(1):17-28. doi: 10.1007/s13402-013-0159-z. Epub 2013 Nov 26.
Studies on the expression of thymidylate synthase (TS) in colorectal cancers (CRCs) have failed to provide unequivocal prognostic or predictive information. Here, we assessed the prognostic significance of TS expression in Astler-Coller stage B2 and C CRCs defined by a p21(WAF1)/p53 immunophenotype in patients subjected to 5-fluorouracil (5FU)-based adjuvant therapy.
A cohort of 189 CRCs was asssessed for TS, p21(WAF1) and p53 expression on tissue microarrays using immunohistochemistry, and associations with disease-free survival (DFS) and overall survival (OS) of the patients were assessed using univariate and multivariate analyses.
TS expression led to the stratification of patients with colon cancer, but not rectal cancer, with immunophenotypes other than p21(WAF1)+/p53- (referred to as P&P) into subgroups characterized by a worse (P&P TS+) and a better (P&P TS-) DFS and OS, in univariate (P = 0.006 and P = 0.005, respectively) and multivariate (P = 0.0004 and P = 0.002, respectively) analyses. The p21(WAF1)+/p53- immunophenotype was associated with a favorable prognosis, irrespective of TS expression.
The strong association observed between the P&P TS+ immunophenotype and a worse DFS and OS suggests a predictive significance of TS expression for 5FU-based adjuvant therapy in patients with colon cancers exhibiting the P&P immunophenotype. In addition, our findings suggest that the appropriate target for assessment of TS expression as a prognostic/predictive marker is a subgroup of colon cancers with an immunophenotype other than p21(WAF1)+/p53-, and that only in this subgroup high TS expression is associated with an unfavorable DFS and OS. Therefore, we suggest that assessing TS expression in conjunction with p21(WAF1)/p53 immunophenotyping of colon cancers may improve the selection of patients suitable for 5FU-based adjuvant chemotherapy.
关于胸苷酸合成酶（TS）在结直肠癌（CRC）中的表达研究未能提供明确的预后或预测信息。在此，我们评估了在接受基于5-氟尿嘧啶（5FU）的辅助治疗的患者中，TS表达在由p21（WAF1）/p53免疫表型定义的Astler-Coller B2期和C期CRC中的预后意义。
使用免疫组织化学对189例CRC患者的组织芯片进行TS、p21（WAF1）和p53表达评估，并通过单因素和多因素分析评估其与患者无病生存期（DFS）和总生存期（OS）的相关性。
在单因素分析（分别为P = 0.006和P = 0.005）和多因素分析（分别为P = 0.0004和P = 0.002）中，TS表达导致结肠癌患者（而非直肠癌患者）根据除p21（WAF1）+/p53-（称为P&P）之外的免疫表型分层为预后较差（P&P TS+）和较好（P&P TS-）的DFS和OS亚组。无论TS表达如何，p21（WAF1）+/p53-免疫表型均与良好预后相关。
观察到P&P TS+免疫表型与较差的DFS和OS之间存在强关联，这表明TS表达对于表现出P&P免疫表型的结肠癌患者基于5FU的辅助治疗具有预测意义。此外，我们的研究结果表明，将TS表达作为预后/预测标志物进行评估的合适靶点是免疫表型不是p21（WAF1）+/p53-的结肠癌亚组，并且仅在该亚组中，高TS表达与不良的DFS和OS相关。因此，我们建议结合结肠癌的p21（WAF1）/p53免疫表型分析来评估TS表达，这可能会改善适合基于5FU的辅助化疗患者的选择。
