Jou Yeong-Chin, Tung Chun-Liang, Tsai Yuh-Shyan, Shen Cheng-Huang, Syue-Yi Chen, Shiau Ai-Li, Tsai Hsin-Tzu, Wu Chao-Liang, Tzai Tzong-Shin
Department of Urology, Chia-Yi Christian Hospital, Chia-Yi, Taiwan.
Urology. 2009 Oct;74(4):951-7. doi: 10.1016/j.urology.2008.11.060. Epub 2009 Aug 13.
To investigate the prognostic role of prothymosin-alpha (PTMA) expression in human upper urinary tract transitional cell carcinoma (UUT-TCC).
Paraffin-embedded tissues were collected from 91 patients with UUT-TCC and from 15 paired normal renal cortex and 13 paired urothelial walls. The primary antibody for PTMA (2F11) used was validated in 4 human urothelial cancer cell lines before assessing the surgical specimen. Immunohistochemistry was then conducted to determine the expression intensity of PTMA, the calculation of immunostaining density using imaging analysis, and for immunostaining localization. The correlates with clinicopathologic characteristics and patient survival were explored.
The expression intensity of PTMA demonstrated a significant enhancement of PTMA expression in UUT-TCCs compared with both paired normal tissues (P = .0002 and P = .0004 for UUT-TCC vs the urothelial wall and vs the renal cortex, respectively). As for the localization of PTMA immunoreactivity, of the 91 tumor specimens, 33 (36.3%) were cytoplasmic PTMA-expressing, 51 (56.0%) were nuclear PTMA-expressing, and 7 (7.7%) were PTMA-negative tumors. On univariate and multivariate analyses, PTMA expression localization was the sole independent prognostic indicator for recurrence-free survival (hazard ratio 4.90, 95% confidence interval 1.73-13.9; P = .003), although pathologic staging was an independent prognostic indicator for both progression-free survival (hazard ratio 22.6, 95% confidence interval 2.56-198; P = .005) and disease-specific overall survival (hazard ratio 5.60, 95% confidence interval 1.48-21.2; P = .011). The limitations of our study included small patient numbers and short follow-up.
The results of our study have shown that PTMA is overexpressed in UUT-TCCs and that cytoplasmic PTMA expression can provide significant prognostic information for subsequent tumor recurrence in the residual urinary tract after nephroureterectomy.
探讨前胸腺素α（PTMA）表达在人上尿路移行细胞癌（UUT-TCC）中的预后作用。
收集91例UUT-TCC患者的石蜡包埋组织，以及15对正常肾皮质和13对尿路上皮壁组织。在评估手术标本前，所用的PTMA（2F11）一抗在4种人尿路上皮癌细胞系中进行了验证。然后进行免疫组织化学以确定PTMA的表达强度，使用图像分析计算免疫染色密度，并进行免疫染色定位。探讨其与临床病理特征及患者生存的相关性。
与配对的正常组织相比，UUT-TCC中PTMA的表达强度显著增强（UUT-TCC与尿路上皮壁及肾皮质相比，P分别为0.0002和0.0004）。至于PTMA免疫反应性的定位，在91个肿瘤标本中，33个（36.3%）为细胞质PTMA表达，51个（56.0%）为细胞核PTMA表达，7个（7.7%）为PTMA阴性肿瘤。单因素和多因素分析显示，PTMA表达定位是无复发生存的唯一独立预后指标（风险比4.90，95%置信区间1.73 - 13.9；P = 0.003），尽管病理分期是无进展生存（风险比22.6，95%置信区间2.56 - 198；P = 0.005）和疾病特异性总生存（风险比5.60，95%置信区间1.48 - 21.2；P = 0.011）的独立预后指标。本研究的局限性包括患者数量少和随访时间短。
我们的研究结果表明，PTMA在UUT-TCC中过表达，并且细胞质PTMA表达可为肾输尿管切除术后残余尿路中后续肿瘤复发提供重要的预后信息。
