Department of Urology, College of Medicine and Hospital, National Cheng Kung University, #138, Sheng-Li Road, Tainan, 70403, Taiwan,
Virchows Arch. 2014 Jun;464(6):717-24. doi: 10.1007/s00428-014-1578-6. Epub 2014 Apr 15.
In this paper, we report a study on the clinical relevance of prothymosin-α expression and its correlation with intratumoral Foxp3(+) and CD8(+) lymphocytes (Foxp3(+)TIL and CD8(+)TIL) in bladder cancer patients. We used immunohistochemical staining for prothymosin-α, Foxp3, and CD8 on 101 tumor specimens harvested by endoscopic resection. The results were correlated with clinicopathological variables and clinical outcome in bladder cancer patients, particularly in 73 patients with superficial disease, using the log-rank test and Cox proportional hazard model. Overall, of the tumors, 30 % were negative, 34 % showed nuclear, and 37 % showed cytoplasmic prothymosin-α expression. Foxp3(+)TILs were detected in 11 % of patients (nonnuclear vs. nuclear, p = 0.096). Patients with a history of urothelial carcinoma have a higher frequency of nonnuclear prothymosin-α expression than those without (p = 0.016, chi-square test). By univariate and multivariate analyses of cases with superficial disease, grade and stage were identified as independent predictors for recurrence-free survival (p = 0.016 and 0.016, respectively). Higher stage and nonnuclear prothymosin-α expression independently predict shorter progression-free survival (p = 0.006 and 0.043, respectively). The presence of Foxp3(+)TILs was significantly associated with disease progression by univariate analysis (p = 0.022), but not by multivariate analysis (p = 0.147). In vitro assays showed that J82 cells which express ectopically nuclear prothymosin-α exhibit higher growth rate and secrete less TGF-β1 than those with cytoplasmic expression or control cells. Altogether, prothymosin-α expression is a determinant of disease progression in superficial bladder cancer. Foxp3(+)TILs tend to be found more often in bladder cancer with nonnuclear prothymosin-α expression. Future study is required to unravel their interaction.
在这项研究中，我们报告了 prothymosin-α 表达的临床相关性及其与膀胱癌患者肿瘤内 Foxp3(+)和 CD8(+)淋巴细胞（Foxp3(+)TIL 和 CD8(+)TIL）的相关性。我们使用免疫组织化学染色法对 101 例经内镜切除的肿瘤标本进行了 prothymosin-α、Foxp3 和 CD8 的检测。使用对数秩检验和 Cox 比例风险模型，将结果与膀胱癌患者的临床病理变量和临床结果相关联，特别是与 73 例浅表性疾病患者相关联。总的来说，在 30%的肿瘤中，细胞核呈阴性，34%呈核 prothymosin-α 表达，37%呈细胞质 prothymosin-α 表达。在 11%的患者中检测到 Foxp3(+)TIL（非核与核，p=0.096）。有尿路上皮癌病史的患者核 prothymosin-α 表达的频率高于无尿路上皮癌病史的患者（p=0.016，卡方检验）。对浅表性疾病患者进行单因素和多因素分析，确定分级和分期是无复发生存率的独立预测因素（p=0.016 和 0.016）。较高的分期和非核 prothymosin-α 表达独立地预测无进展生存期较短（p=0.006 和 0.043）。Foxp3(+)TIL 的存在通过单因素分析与疾病进展显著相关（p=0.022），但通过多因素分析不相关（p=0.147）。体外实验表明，表达异位核 prothymosin-α的 J82 细胞比表达细胞质 prothymosin-α或对照细胞具有更高的生长速度和更少的 TGF-β1 分泌。总之，prothymosin-α 表达是浅表性膀胱癌疾病进展的决定因素。Foxp3(+)TIL 往往在非核 prothymosin-α表达的膀胱癌中更常见。需要进一步的研究来揭示它们的相互作用。
