胸苷酸合成酶在膀胱尿路上皮癌中的表达及预后价值

Expression of thymidylate synthase in bladder urothelial carcinoma and its prognostic value

目的 探讨胸苷酸合成酶（TS）在膀胱尿路上皮癌（BUC）的表达情况及临床意义，评价TS预后价值，为肿瘤预后判断及治疗方案的选择提供帮助。方法采用免疫组织化学染色（sP法）的方法检测54例BUC组织及15例正常膀胱组织的髑表达，通过回顾性随访，了解患者术后情况。以髑表达水平、临床病理变量及两个预后变量[无复发生存率（RFS）和总生存率（OS）]作为研究对象，探讨它们之间的关系，绘制生存曲线，进行Cox回归分析。结果54例肿瘤标本中Ts高表达率为46．30％（25／54），其中G1级为29．41％（5／17），G2级为46．43％（13／28），G3级为77．78％（7／9）；Ta期为21．43％（3／14），T1期为26．32％（5／19），T2期为86．67％（13／15），T3期为66．67％（2／3），T4期为66．67％（2／3）；TS表达水平与肿瘤分级、分期呈正相关（Kruskal—WallisH，P=0．03，P〈0．001）。TS高表达患者术后复发率、病死率分别为60．00％（15／25）和44．00％（11／25），经生存分析和Cox回归分析，肿瘤的Ts表达水平是术后复发（RR为2．65，95％C10．80～8．81，P〈0．05）、死亡（RR为1．42，95％C10．36～5．58，P〈0．05）的独立预后因素。结论随着Ts表达水平升高，BUC发生恶性进展和复发的概率增加，测定其表达水平有助于选择恰当的治疗和随访方案。

Objective To investigate the expression of thymidylate synthase （TS） in bladder urothelial careinoma（BUC） and its clinical significance, and to evaluate its prognostic value, thus to help predict the prognosis and choose therapy protocal. Methods The expression of ＂IS was assessed by immunohistochemistry in 54 BUC and 15 normal bladder specimens, and all these clinical data were retrospectively analyzed after surgery. Expression of TS, clinicopathologic findings and two prognostic variances （ relapse-free survival （RFS） and overall survival （OS）） were determined. The prognostic value of TS was estimated by survival curve and Cox proportional hazards model. Results lmmunohistochemistry showed that 25 of 54 BUC cases （46. 30% ） had high TS expression. In these cases,there was 29.41% （5/17） for G1,46. 43% （13/28） for G2,77.78% （7/9） for G3 ;21.43% （3/14） for Ta, 26. 32% （5/19） for T1,86. 67% （ 13/15 ） for T2,66. 67% （ 2/3 ） for T3, 66. 67% （2/3） for T4. Expression of TS was positively associated with the grade and stage of earcinorma （ Kruskal - Wallis H , P = 0. 0 3 and P 〈 0. 001 ） . The recurrence and case - fatality of patients with high TS expression was 60. 00% （ 15/25 ） and 44. 00% （ 11/25 ）, respectively. The survival analysis and Cox regression analysis showed that expression of TS were independent predictor for recurrence （ RR = 2.65,95% CI was 0.80-8.81,P〈0.05） and death （RR=1.42,95%Clwas 0.36-5.58,P〈0.05）. Conclusions The probability of BUC progress and recurrence increases with the increasing of TS expression. Detection of ＂IS expressing level can contribute to select appropriate treatment and follow-up schema.