Loss of nuclear prothymosin-α expression is associated with disease progression in human superficial bladder cancer

Yuh-Shyan Tsai, Yeong Chin Jou, Chun Liang Tung, Chang Te Lin, Cheng Huang Shen, Syue Yi Chen, Hsin Tzu Tsai, Chen Li Lai, Chao-Liang Wu, Tzong Shin Tzai

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)717-724
Number of pages8
JournalVirchows Archiv
Volume464
Issue number6
DOIs
Publication statusPublished - 2014 Jan 1

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Urinary Bladder Neoplasms
Disease Progression
Multivariate Analysis
Chi-Square Distribution
Proportional Hazards Models
Disease-Free Survival
Neoplasms
Lymphocytes
Staining and Labeling
Carcinoma
Recurrence
Survival
Growth

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Tsai, Yuh-Shyan ; Jou, Yeong Chin ; Tung, Chun Liang ; Lin, Chang Te ; Shen, Cheng Huang ; Chen, Syue Yi ; Tsai, Hsin Tzu ; Lai, Chen Li ; Wu, Chao-Liang ; Tzai, Tzong Shin. / Loss of nuclear prothymosin-α expression is associated with disease progression in human superficial bladder cancer. In: Virchows Archiv. 2014 ; Vol. 464, No. 6. pp. 717-724.
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abstract = "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.",
author = "Yuh-Shyan Tsai and Jou, {Yeong Chin} and Tung, {Chun Liang} and Lin, {Chang Te} and Shen, {Cheng Huang} and Chen, {Syue Yi} and Tsai, {Hsin Tzu} and Lai, {Chen Li} and Chao-Liang Wu and Tzai, {Tzong Shin}",
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Loss of nuclear prothymosin-α expression is associated with disease progression in human superficial bladder cancer. / Tsai, Yuh-Shyan; Jou, Yeong Chin; Tung, Chun Liang; Lin, Chang Te; Shen, Cheng Huang; Chen, Syue Yi; Tsai, Hsin Tzu; Lai, Chen Li; Wu, Chao-Liang; Tzai, Tzong Shin.

In: Virchows Archiv, Vol. 464, No. 6, 01.01.2014, p. 717-724.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Loss of nuclear prothymosin-α expression is associated with disease progression in human superficial bladder cancer

AU - Tsai, Yuh-Shyan

AU - Jou, Yeong Chin

AU - Tung, Chun Liang

AU - Lin, Chang Te

AU - Shen, Cheng Huang

AU - Chen, Syue Yi

AU - Tsai, Hsin Tzu

AU - Lai, Chen Li

AU - Wu, Chao-Liang

AU - Tzai, Tzong Shin

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

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