Davies M M, Johnston P G, Kaur S, Allen-Mersh T G
Department of Gastrointestinal Surgery, Imperial College School of Medicine, Chelsea and Westminster Hospital, London, United Kingdom.
Clin Cancer Res. 1999 Feb;5(2):325-8.
We assessed whether intensity of colorectal liver metastasis staining with the thymidylate synthase (TS) antibody TS106 predicted response to hepatic arterial infusion (HAI) of floxuridine chemotherapy. Liver metastasis biopsies were taken during laparotomy for hepatic arterial cannulation and stained using the TS106 monoclonal antibody. Staining intensity was designated at histological examination by two independent assessors as either "high" or "low." Patients were treated by HAI, and liver metastasis response was assessed by comparison of computed tomography scan tumor volume before and after 4 months of treatment. A significant correlation (Fisher's exact test, P = 0.01) was noted between partial response to HAI and TS106 staining intensity in patients with colorectal liver metastases. Seventy-five percent of patients with evidence of a partial response had low TS staining compared with 29% of nonresponders. There was a significant difference (Fisher's exact test, P = 0.01) in the proportion of low (9 of 16) compared with high (3 of 20) TS staining tumors in which a partial response occurred. There was no significant difference (logrank test, P = 0.4) in survival from hepatic cannulation and HAI treatment of high (median, 322 days; interquartile range, 236-411) compared with low (median, 335 days; interquartile range, 301-547) TS staining patients. This study demonstrates an inverse correlation between TS immunohistochemical staining intensity in colorectal liver metastases and response to HAI. The results suggest that a prospective assessment of TS staining intensity in colorectal liver metastases would be useful to determine whether this method can be used to define patients who will benefit from HAI chemotherapy.
我们评估了用胸苷酸合成酶（TS）抗体TS106对结直肠癌肝转移灶进行染色的强度是否可预测对氟尿苷肝动脉灌注（HAI）化疗的反应。在剖腹手术进行肝动脉插管时获取肝转移灶活检组织，并用TS106单克隆抗体进行染色。在组织学检查中，由两名独立的评估者将染色强度指定为“高”或“低”。患者接受HAI治疗，并通过比较治疗4个月前后的计算机断层扫描肿瘤体积来评估肝转移灶的反应。在结直肠癌肝转移患者中，观察到HAI的部分反应与TS106染色强度之间存在显著相关性（Fisher精确检验，P = 0.01）。有部分反应证据的患者中，75%的TS染色为低，而无反应者中这一比例为29%。出现部分反应的低TS染色肿瘤（16例中的9例）与高TS染色肿瘤（20例中的3例）的比例存在显著差异（Fisher精确检验，P = 0.01）。高TS染色患者（中位生存期322天；四分位间距236 - 411天）与低TS染色患者（中位生存期335天；四分位间距301 - 547天）在肝插管和HAI治疗后的生存期无显著差异（对数秩检验，P = 0.4）。本研究表明结直肠癌肝转移灶中TS免疫组化染色强度与对HAI的反应呈负相关。结果提示，对结直肠癌肝转移灶中TS染色强度进行前瞻性评估，对于确定该方法是否可用于界定将从HAI化疗中获益的患者可能是有用的。
