Abstract：
BACKGROUND: High-grade urothelial carcinoma either non-Schistosoma (NS-UBC) or Schistosoma (S-UBC)-associated is the tenth cause of death worldwide and represents a serious therapeutic problem.
OBJECTIVE: Evaluation of the immmunohistochemical expression of tumor necrosis factor-alpha (TNFα), epidermal growth factor receptor (EGFR), programmed cell death protein-1 (PDL1), estrogen receptor-alpha (ERα) and UroplakinIII, in the high-grade in NS-UBC and S-UBC as potential prognostic and therapeutic targets analyzed through estimation of area percentage, optical density and international pathological scoring system for each marker.
METHODS: Sixty high grade urothelial carcinoma cases were enrolled in the study (30 cases of NS-UBC and 30 cases of S-UBC). The cases were immunohistochemically-assessed for TNFα, EGFR, PDL1, ERα and Uroplakin III expression. In S-UBC, parasite load was also evaluated for correlation with the immunohistochemical markers\' expression in S-UBC.
RESULTS: The area percentage of immune-expression of TNFα and EGFR was higher in S-UBC compared to NS-UBC. On the other hand, the NS-UBC displayed statistically-higher expression of PDL1 and uroplakinIII (p-value <0.001). ERα revealed higher, yet, non-significant expressions in S-UBC compared to NS-UBC (p-value =0.459). PDL1 expression showed the most superior record regarding area percentage (64.6± 34.5). Regarding optical density, TNF-α showed the highest transmittance expression (2.4 ± 0.9). EGFR positively correlated with PDL1 in S-UBC (r= 0.578, p-value =0.001) whereas in NS-UBC, TNFα and PDL1 (r=0.382, p-value=0.037) had positive correlation. Schistosoma eggs in tissues oppose uroplakin III expression and trigger immunomodulation via PDL1.
CONCLUSIONS: Due to lower UroplakinIII expression, S-UBC is supposed to have a poorer prognosis. Hormonal therapy is not hypothesized due to a very minimal ERα expression in both NS-UBC and S-UBC. Regarding immunotherapy, anti-TNF-α is suggested for S-UBC whilst in NS-UBC, blockading PDL1 might be useful. Targeted EGFR therapy seems to carry emphasized outcomes in S-UBC. Correlations encourage combined immune therapy in NS-UBC; nevertheless, in S-UBC, combined anti-EGFR and PDL1 seem to be of benefit.
OBJECTIVE: Evaluation of the immmunohistochemical expression of tumor necrosis factor-alpha (TNFα), epidermal growth factor receptor (EGFR), programmed cell death protein-1 (PDL1), estrogen receptor-alpha (ERα) and UroplakinIII, in the high-grade in NS-UBC and S-UBC as potential prognostic and therapeutic targets analyzed through estimation of area percentage, optical density and international pathological scoring system for each marker.
METHODS: Sixty high grade urothelial carcinoma cases were enrolled in the study (30 cases of NS-UBC and 30 cases of S-UBC). The cases were immunohistochemically-assessed for TNFα, EGFR, PDL1, ERα and Uroplakin III expression. In S-UBC, parasite load was also evaluated for correlation with the immunohistochemical markers\' expression in S-UBC.
RESULTS: The area percentage of immune-expression of TNFα and EGFR was higher in S-UBC compared to NS-UBC. On the other hand, the NS-UBC displayed statistically-higher expression of PDL1 and uroplakinIII (p-value <0.001). ERα revealed higher, yet, non-significant expressions in S-UBC compared to NS-UBC (p-value =0.459). PDL1 expression showed the most superior record regarding area percentage (64.6± 34.5). Regarding optical density, TNF-α showed the highest transmittance expression (2.4 ± 0.9). EGFR positively correlated with PDL1 in S-UBC (r= 0.578, p-value =0.001) whereas in NS-UBC, TNFα and PDL1 (r=0.382, p-value=0.037) had positive correlation. Schistosoma eggs in tissues oppose uroplakin III expression and trigger immunomodulation via PDL1.
CONCLUSIONS: Due to lower UroplakinIII expression, S-UBC is supposed to have a poorer prognosis. Hormonal therapy is not hypothesized due to a very minimal ERα expression in both NS-UBC and S-UBC. Regarding immunotherapy, anti-TNF-α is suggested for S-UBC whilst in NS-UBC, blockading PDL1 might be useful. Targeted EGFR therapy seems to carry emphasized outcomes in S-UBC. Correlations encourage combined immune therapy in NS-UBC; nevertheless, in S-UBC, combined anti-EGFR and PDL1 seem to be of benefit.
摘要：
背景：非血吸虫（NS-UBC）或血吸虫（S-UBC）相关的高级别尿路上皮癌是全球第十个死亡原因，代表了严重的治疗问题。
目的：肿瘤坏死因子α（TNFα）免疫组织化学表达的评估，表皮生长因子受体（EGFR），程序性细胞死亡蛋白-1（PDL1），雌激素受体α（ERα）和UroplakinIII，在NS-UBC和S-UBC的高级别作为潜在的预后和治疗目标，通过估计面积百分比进行分析，每个标记物的光密度和国际病理评分系统。
方法：60例高级别尿路上皮癌（NS-UBC30例，S-UBC30例）。对这些病例进行了TNFα的免疫组织化学评估，EGFR,PDL1、ERα和UroplakinIII表达。在S-UBC,还评估了寄生虫负荷与S-UBC中免疫组织化学标记表达的相关性。
结果：与NS-UBC相比，S-UBC中TNFα和EGFR的免疫表达面积百分比更高。另一方面,NS-UBC显示PDL1和尿plakinIII的表达在统计学上较高(p值<0.001)。ERα显示更高，然而，S-UBC与NS-UBC相比无显著表达(p值=0.459)。PDL1表达在面积百分比方面表现出最好的记录（64.6±34.5）。关于光密度，TNF-α显示最高的透射率表达（2.4±0.9）。EGFR在S-UBC中与PDL1呈正相关(r=0.578,p值=0.001),而在NS-UBC中,TNFα与PDL1呈正相关(r=0.382,p值=0.037)。组织中的血吸虫卵反对尿plakinIII表达并通过PDL1触发免疫调节。
结论：由于UroplakinIII表达较低，S-UBC预后较差。由于NS-UBC和S-UBC中的ERα表达非常小,因此不假设激素治疗。关于免疫疗法，抗TNF-α建议用于S-UBC，而在NS-UBC中，阻塞PDL1可能是有用的。靶向EGFR治疗似乎在S-UBC中具有强调的结果。相关性鼓励NS-UBC的联合免疫治疗；尽管如此，在S-UBC,联合使用抗EGFR和PDL1似乎是有益的。
目的：肿瘤坏死因子α（TNFα）免疫组织化学表达的评估，表皮生长因子受体（EGFR），程序性细胞死亡蛋白-1（PDL1），雌激素受体α（ERα）和UroplakinIII，在NS-UBC和S-UBC的高级别作为潜在的预后和治疗目标，通过估计面积百分比进行分析，每个标记物的光密度和国际病理评分系统。
方法：60例高级别尿路上皮癌（NS-UBC30例，S-UBC30例）。对这些病例进行了TNFα的免疫组织化学评估，EGFR,PDL1、ERα和UroplakinIII表达。在S-UBC,还评估了寄生虫负荷与S-UBC中免疫组织化学标记表达的相关性。
结果：与NS-UBC相比，S-UBC中TNFα和EGFR的免疫表达面积百分比更高。另一方面,NS-UBC显示PDL1和尿plakinIII的表达在统计学上较高(p值<0.001)。ERα显示更高，然而，S-UBC与NS-UBC相比无显著表达(p值=0.459)。PDL1表达在面积百分比方面表现出最好的记录（64.6±34.5）。关于光密度，TNF-α显示最高的透射率表达（2.4±0.9）。EGFR在S-UBC中与PDL1呈正相关(r=0.578,p值=0.001),而在NS-UBC中,TNFα与PDL1呈正相关(r=0.382,p值=0.037)。组织中的血吸虫卵反对尿plakinIII表达并通过PDL1触发免疫调节。
结论：由于UroplakinIII表达较低，S-UBC预后较差。由于NS-UBC和S-UBC中的ERα表达非常小,因此不假设激素治疗。关于免疫疗法，抗TNF-α建议用于S-UBC，而在NS-UBC中，阻塞PDL1可能是有用的。靶向EGFR治疗似乎在S-UBC中具有强调的结果。相关性鼓励NS-UBC的联合免疫治疗；尽管如此，在S-UBC,联合使用抗EGFR和PDL1似乎是有益的。
