原发性结直肠癌中胸苷酸合成酶、胸苷磷酸化酶、VEGF 和 p53 蛋白的表达对预测氟尿嘧啶为基础的化疗反应的价值。

Thymidylate synthase, thymidine phosphorylase, VEGF and p53 protein expression in primary colorectal cancer for predicting response to 5-fluorouracil-based chemotherapy.

机构信息

Department of Internal Medicine, College of Medicine, Hanyang University, Seoul, Korea.

出版信息

Cancer Res Treat. 2005 Aug;37(4):216-22. doi: 10.4143/crt.2005.37.4.216. Epub 2005 Aug 31.

DOI:10.4143/crt.2005.37.4.216

PMID:19956517

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2785918/

Abstract

PURPOSE

In the treatment of advanced metastatic colorectal cancer, several new agents, such as irinotecan and oxaliplatin, have been developed, which have improved both disease free and overall survivals. Among these agents, 5-fluorouracil (5-FU) still remains one of the most active agents, and the selection of patients who can benefit from 5-FU-based chemotherapy is still important, as those unlikely to benefit could be spared the harmful side effects. The expression levels of thymidylate synthase (TS), thymidine phosphorylase (TP) and p53 have been known to be associated with the clinical response to 5-FU-based therapy as well as the prognosis, and that of vascular endothelial growth factor (VEGF) is associated with poor survival.

MATERIALS AND METHODS

The relationship between the expressions of TS, TP, VEGF and p53 in primary tumors, using immunohistochemistry, and the response of 45 metastatic colorectal cancer patients (M:F=25:20, median age 59 yrs) to 5-FU-based chemotherapy were evaluated.

RESULTS

Thirty-seven patients were treated with 5-FU/LV/irinotecan (FOLFIRI) and 8 with 5-FU/LV/oxaplatin (FOLFOX). The overall response rate was 28.9% (13/45). When immunohistochemically analyzed with monoclonal antibodies against TS, TP, VEGF and p53, 55.6% of the patients (25/45) were positive for TS, 48.9% (22/45) for TP, 82.2% (37/45) for VEGF, and 80% (36/45) for p53. There was a significant difference in the intensity of TS expression between the clinical responders and non-responders (p=0.036). In terms of the staining pattern of TS expression, diffuse staining was correlated with a poor response (p=0.012) and poor survival (p=0.045). However, there was no correlation between the expressions of TP, VEGF or P53 and the response to chemotherapy.

CONCLUSION

These results suggest that the expression of TS in primary colorectal cancer might be an important prognostic factor for chemotherapy response and survival, and might be a useful therapeutic marker for the response of chemotherapy.

摘要

目的

在晚期转移性结直肠癌的治疗中，已经开发了几种新的药物，如伊立替康和奥沙利铂，这提高了无病生存期和总生存期。在这些药物中，5-氟尿嘧啶（5-FU）仍然是最有效的药物之一，选择可能受益于 5-FU 为基础的化疗的患者仍然很重要，因为那些不太可能受益的患者可以避免有害的副作用。胸苷酸合成酶（TS）、胸苷磷酸化酶（TP）和 p53 的表达水平与 5-FU 为基础的治疗的临床反应以及预后相关，血管内皮生长因子（VEGF）的表达与生存不良相关。

材料和方法

使用免疫组织化学方法评估了原发肿瘤中 TS、TP、VEGF 和 p53 的表达与 45 例转移性结直肠癌患者（M：F=25:20，中位年龄 59 岁）对 5-FU 为基础的化疗反应之间的关系。

结果

37 例患者接受了 5-FU/LV/伊立替康（FOLFIRI）治疗，8 例患者接受了 5-FU/LV/奥沙利铂（FOLFOX）治疗。总体缓解率为 28.9%（13/45）。当用针对 TS、TP、VEGF 和 p53 的单克隆抗体进行免疫组织化学分析时，45 例患者中有 55.6%（25/45）的 TS 阳性，48.9%（22/45）的 TP 阳性，82.2%（37/45）的 VEGF 阳性，80%（36/45）的 p53 阳性。在临床反应者和无反应者之间，TS 表达强度存在显著差异（p=0.036）。在 TS 表达模式方面，弥漫性染色与不良反应（p=0.012）和不良生存（p=0.045）相关。然而，TP、VEGF 或 P53 的表达与化疗反应之间没有相关性。