Correlation of cyclooxygenase-2 expression with molecular markers, pathological features and clinical outcome of transitional cell carcinoma of the bladder
Correlation of cyclooxygenase-2 expression with molecular markers, pathological features and clinical outcome of transitional cell carcinoma of the bladder
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DOI：
10.1097/01.ju.0000080401.85145.ee
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发表时间：
2003-09-01
影响因子：
6.6
通讯作者：
Lerner, SP
中科院分区：
文献类型：
--
作者：
Shariat, SF;Matsumoto, K;Lerner, SP
目的：我们研究了环氧化酶-2（考克斯-2）表达与膀胱移行细胞癌（TCC）中常见的分子改变之间的关系，并确定考克斯-2免疫反应性是否与接受根治性膀胱切除术的患者的癌症分期、进展和生存率相关。免疫组化染色考克斯-2在档案肿瘤标本从80例接受根治性膀胱癌。免疫反应性被分类为阳性（超过10%的肿瘤细胞具有反应性）或阴性。结果：COX-2在62例（78%）患者中表达过强，其中12例（78%）患者的COX-2表达明显高于正常对照组（P < 0. 05），其余12例（78%）患者的COX-2表达明显高于正常对照组（P < 0. 05）。考克斯-2过度表达与肌肉浸润性病理分期（p = 0.022）、TGF-β 1过度表达（p = 0.004）、E-钙粘蛋白表达减少（p < 0.001）以及pRB（p = 0.003）和p16（p = 0.006）表达改变相关。中位随访时间为101个月，考克斯-2过度表达与疾病进展（p = 0.038）和膀胱癌特异性生存（p = 0.042）相关。然而，当调整标准病理特征的影响时，仅淋巴结转移与膀胱癌进展（p = 0.027）和死亡率（p = 0.042）相关。结论：考克斯-2在膀胱TCC患者中普遍表达。使用10%的截断值，异常考克斯-2表达与侵袭程度、TGF-β 1和pRB/p16通路的改变以及细胞粘附的丧失相关。虽然考克斯-2表达对膀胱TCC患者的预后价值有限，但它可能作为选择性考克斯-2抑制剂治疗的靶点。
Purpose: We investigated the relationship between cyclooxygenase-2 (COX-2) expression and molecular alterations commonly found in transitional cell carcinoma (TCC) of the bladder and determined whether COX-2 immunoreactivity is associated with cancer stage, progression and survival in patients undergoing radical cystectomy.Materials and Methods: Immunohistochemical staining for COX-2 was done in archival tumor specimens from 80 patients who underwent radical cystectomy. Immunoreactivity was categorized as positive (reactivity in greater than 10% tumor cells) or negative. Microvessel density, E-cadherin, pRB, p16, p21, p53 and transforming growth factor (TGF)-beta1 and its receptors (types I and II) were also studied because evidence suggests a biological association between COX-2 and alteration of these molecules.Results: COX-2 was over expressed in 62 patients (78%). COX-2 over expression was associated with muscle invasive pathological stage (p = 0.022), TGF-beta1 over expression (p = 0.004), decreased E-cadherin expression (p < 0.001), and altered expression of pRB (p = 0.003) and p16 (p = 0.006). At a median followup of 101 months COX-2 over expression was associated with disease progression (p = 0.038) and bladder cancer specific survival (p = 0.042). However, when adjusted for the effects of standard pathological features, only lymph node metastasis was associated with bladder cancer progression (p = 0.027) and mortality (p = 0.042).Conclusions: COX-2 is commonly expressed in patients with bladder TCC. Using the cutoff of 10% abnormal COX-2 expression is associated with the degree of invasiveness, alterations in TGF-beta1 and pRB/p16 pathways, and loss of cell adhesion. While COX-2 expression has limited prognostic value in patients with bladder TCC, it may serve as a target for therapy with selective COX-2 inhibitors.