PTP4A3独立预测根治性肾输尿管切除术治疗的上尿路尿路上皮癌的转移和生存情况。
PTP4A3 Independently Predicts Metastasis and Survival in Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy.
作者信息
Yeh Hsin-Chih, Li Ching-Chia, Huang Chun-Nung, Hour Tzyh-Chyuan, Yeh Bi-Wen, Li Wei-Ming, Liang Peir-In, Chang Lin-Li, Li Chien-Feng, Wu Wen-Jeng
机构信息
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.
Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
出版信息
J Urol. 2015 Nov;194(5):1449-55. doi: 10.1016/j.juro.2015.05.101. Epub 2015 Jun 10.
PURPOSE
Increasing evidence has shown that protein tyrosine phosphatases have dominant roles in setting the levels of tyrosine phosphorylation and promoting oncogenic processes. PTP4A3 has been implicated in cancer metastasis but to our knowledge the role of PTP4A3 in upper tract urothelial carcinoma is unknown. The aim of this study was to investigate the association of PTP4A3 with disease characteristics, distant metastasis and prognosis of upper tract urothelial carcinoma.
MATERIALS AND METHODS
The importance of PTP4A3 was initially examined in paired normal urothelium, noninvasive upper tract urothelial carcinoma, invasive upper tract urothelial carcinoma and nodal metastatic tissue. The PTP4A3 transcript level was assessed in another 20 upper tract urothelial carcinoma samples by real-time reverse transcriptase-polymerase chain reaction. PTP4A3 protein expression was determined by immunohistochemistry using the H-score in 340 upper tract urothelial carcinoma samples. It was further correlated with clinicopathological factors, and disease specific and metastasis-free survival.
RESULTS
The expression of PTP4A3 significantly increased from normal urothelium, noninvasive upper tract urothelial carcinoma and invasive upper tract urothelial carcinoma to nodal metastatic tissue (p <0.001). The PTP4A3 transcript level was also markedly up-regulated in higher stage upper tract urothelial carcinoma (p = 0.002). Over expression of PTP4A3 protein was significantly associated with advanced pT status, nodal metastasis, lymphovascular invasion and perineural invasion (each p <0.001) as well as with inferior disease specific and metastasis-free survival on multivariate analysis (each p <0.0001). In addition, it predicted metastasis in patients with pTa, pT1 and pT2 upper tract urothelial carcinoma.
CONCLUSIONS
Results imply that PTP4A3 has a role in the carcinogenesis of upper tract urothelial carcinoma. PTP4A3 over expression independently predicted the metastasis and outcome of upper tract urothelial carcinoma, which was even more important in organ confined disease.
目的
越来越多的证据表明，蛋白酪氨酸磷酸酶在设定酪氨酸磷酸化水平和促进致癌过程中起主导作用。PTP4A3与癌症转移有关，但据我们所知，PTP4A3在上尿路尿路上皮癌中的作用尚不清楚。本研究的目的是探讨PTP4A3与上尿路尿路上皮癌的疾病特征、远处转移及预后的关系。
材料与方法
首先在配对的正常尿路上皮、非侵袭性上尿路尿路上皮癌、侵袭性上尿路尿路上皮癌和淋巴结转移组织中检测PTP4A3的重要性。通过实时逆转录聚合酶链反应在另外20例上尿路尿路上皮癌样本中评估PTP4A3转录水平。采用免疫组织化学法测定340例上尿路尿路上皮癌样本中PTP4A3蛋白的表达，并计算H评分。进一步分析其与临床病理因素、疾病特异性生存率和无转移生存率的相关性。
结果
从正常尿路上皮、非侵袭性上尿路尿路上皮癌、侵袭性上尿路尿路上皮癌到淋巴结转移组织，PTP4A3的表达显著增加（p<0.001）。在高分期上尿路尿路上皮癌中，PTP4A3转录水平也明显上调（p = 0.002）。PTP4A3蛋白的过度表达与晚期pT状态、淋巴结转移、淋巴管浸润和神经周围浸润显著相关（各p<0.001），多因素分析显示其与疾病特异性生存率和无转移生存率较低也显著相关（各p<0.0001）。此外，它还可预测pTa、pT1和pT2期上尿路尿路上皮癌患者的转移情况。
结论
结果表明PTP4A3在上尿路尿路上皮癌的发生中起作用。PTP4A3的过度表达独立预测上尿路尿路上皮癌的转移和预后，这在器官局限性疾病中更为重要。
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