Wong N A, Brett L, Stewart M, Leitch A, Longley D B, Dunlop M G, Johnston P G, Lessells A M, Jodrell D I
Department of Pathology, University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG.
Br J Cancer. 2001 Dec 14;85(12):1937-43. doi: 10.1054/bjoc.2001.2175.
Thymidylate synthase (TS) is a key enzyme in DNA synthesis and is inhibited by metabolites of the chemotherapeutic agent 5-fluorouracil (5FU). Nuclear expression of TS in human tissue in vivo has not been characterised and its clinicopathological correlates in malignancy are unknown. 52 cases of primary colorectal carcinoma (CRC) and 24 cases of matched metastatic carcinoma were studied immunohistochemically using the monoclonal antibody TS106. The degree of nuclear TS immunostaining correlated closely with levels of TS mRNA expression amongst 10 CRCs studied. Strong nuclear immunostaining was seen in normal basal crypt colonocytes and germinal centre cells, and in a varying proportion of adenocarcinoma cells. Amongst the primary carcinomas, higher TS nuclear expression was associated with prominent extracellular mucin production and right-sided location. Higher TS nuclear expression also showed a significant association with poorer response to protracted venous infusional 5FU therapy. There was no clear association between TS nuclear expression and Ki67 or p53 expression assessed immunohistochemically. There was a strong positive correlation between TS nuclear expression in primary and metastatic CRC but the latter generally showed higher expression than matched primary tumour tissue. These findings confirm the nuclear expression of TS protein in human cells in vivo and provide new insight into how such expression may relate to the behaviour of CRCs.
胸苷酸合成酶（TS）是DNA合成中的关键酶，可被化疗药物5-氟尿嘧啶（5FU）的代谢产物所抑制。TS在人体组织中的核表达尚未得到表征，其在恶性肿瘤中的临床病理相关性也尚不清楚。使用单克隆抗体TS106对52例原发性结直肠癌（CRC）和24例配对的转移癌进行了免疫组织化学研究。在所研究的10例CRC中，TS核免疫染色程度与TS mRNA表达水平密切相关。在正常的结肠隐窝基底细胞和生发中心细胞以及不同比例的腺癌细胞中可见强核免疫染色。在原发性癌中，较高的TS核表达与突出的细胞外粘蛋白产生和右侧位置相关。较高的TS核表达还显示出与对延长静脉输注5FU治疗的较差反应有显著关联。通过免疫组织化学评估，TS核表达与Ki67或p53表达之间没有明显关联。原发性和转移性CRC中的TS核表达之间存在强正相关，但后者通常比配对的原发性肿瘤组织表达更高。这些发现证实了TS蛋白在体内人体细胞中的核表达，并为这种表达如何与CRC的行为相关提供了新的见解。
