Clinical significance of thymidylate synthase expression in bladder cancer
Clinical significance of thymidylate synthase expression in bladder cancer
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DOI：
10.1046/j.1442-2042.2002.00479.x
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发表时间：
2002-07-01
影响因子：
2.6
通讯作者：
Nomura, Y
中科院分区：
文献类型：
--
作者：
Nomura, T;Nakagawa, M;Nomura, Y
背景：本文旨在探讨胸苷酸合酶（TS）表达在膀胱癌中的临床意义及其与p53、Ki-67、增殖细胞核抗原（PCNA）等增殖标志物的关系。方法：采用逆转录聚合酶链反应（RT-PCR）法，以甘油醛-3-磷酸脱氢酶（GAPDH）为内标，检测54例膀胱癌患者胸苷酸合酶基因的表达情况。标准。还通过免疫组织化学方法检查了 TS 表达。对 p53、Ki-67 和 PCNA 表达进行免疫组织化学研究，以检查肿瘤中 TS 表达与增殖标志物表达之间的相关性。还检查了血管侵犯和远处转移等预后和临床结果因素以及 TS 表达。结果：24 名浸润性膀胱癌患者的 TS 水平为 5.07 +/- 0.77（平均值 +/- SE），而 30 名浅表性膀胱癌患者的 TS 水平为 2.28 +/- 0.38。浸润性膀胱癌和浅表性膀胱癌之间的 TS 水平存在显着差异（P = 0.001）。这些患者中TS表达与p53（r = 0.686，P < 0.01）、Ki-67（r = 0.715，P < 0.0001）或PCNA表达（r = 0.670，P < 0.0001）各增殖标志物呈正相关。 TS水平高（TS≥2.63，中位值）的患者血管侵犯和远处转移的发生率显着较高。 Kaplan-Meier 分析表明，与低 TS 水平的患者（TS < 2.63；P = 0.034）相比，高 TS 水平（TS 大于或等于 2.63）的患者预后较差。此外，高TS染色患者的预后显着差于低染色患者（P = 0.012）。结论：TS表达水平的测定可能有助于选择合适的膀胱癌治疗方案，因为TS表达影响膀胱肿瘤的生物学特性。
Background: The purpose of the present paper was to investigage the clinical significance of thymidylate synthase (TS) expression in bladder cancer and its association with proliferation markers, such as p53, Ki-67, and proliferating cell nuclear antigen (PCNA).Methods: Thymidylate synthase gene expression in 54 patients with bladder cancer was measured by the reverse transcription polymerase chain reaction (RT-PCR) method using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal standard. The TS expression was also examined immunohistochemically. Immunohistochemical studies of p53, Ki-67, and PCNA expression were carried out to examine the correlation between TS expression and the expression of proliferation markers in the tumors. Prognostic and clinical outcome factors such as vascular invasion and distant metastasis were also examined along with TS expression.Results: Twenty-four patients with invasive bladder cancer had TS levels of 5.07 +/- 0.77 (mean +/- SE), while 30 patients with superficial bladder cancer had TS levels of 2.28 +/- 0.38. There was a significant difference in TS levels between invasive and superficial bladder cancer (P = 0.001). There was a positive correlation between TS expression and each proliferation marker of p53 (r = 0.686, P < 0.01), Ki-67 (r = 0.715, P < 0.0001) or PCNA expressions (r = 0.670, P < 0.0001) in these patients. Patients with high TS levels (TS greater than or equal to 2.63, the median value) had significantly higher rates of vascular invasion and distant metastasis. Kaplan-Meier analysis demonstrated that patients with high TS levels (TS greater than or equal to 2.63) had unfavorable prognosis compared to patients with low TS levels (TS < 2.63; P = 0.034). Furthermore, patients with high TS staining had a significantly poorer prognosis than those with low staining (P = 0.012).Conclusion: Determination of level of TS expression may help in the selection of an appropriate treatment for bladder cancer because TS expression influences the biological characteristic of bladder tumor.