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Abstract：
OBJECTIVE: To evaluate the presence and subtypes of tertiary lymphatic structures (TLSs) in urothelial carcinoma of the bladder (UCB) and to analyze their associated clinicopathological characteristics and prognostic significance.
METHODS: The study enrolled 580 patients with surgically treated UCB, including 313 non-muscle invasive bladder cancer (NMIBC) and 267 muscle-invasive bladder cancer (MIBC). The presence and subtypes of TLSs were identified by immunohistochemistry (CD20, CD3, Bcl-6, and CD21). TLSs were classified into non-GC (nGC) TLS and GC TLS subtypes based on germinal center (GC) formation. Disease-free survival (DFS) was used as an endpoint outcome to evaluate the prognostic significance of TLS and its subtypes in UCB.
RESULTS: TLSs were more common in MIBC than in NMIBC (67.8% vs 48.2%, P < .001), and the tumor-infiltrating lymphocyte (TIL) mean density was significantly higher in MIBC than in NMIBC (24.0% vs 17.5%, P < .001). Moreover, a positive correlation was found between TLS presence and GC structure formation and TIL infiltration in UCB. Endpoint events occurred in 191 patients. Compared to patients with endpoint events, patients without disease progression exhibited higher TIL density and more TLSs (P < .05). Kaplan-Meier curves showed that TLS was associated with better DFS in NMIBC (P = .041) and MIBC (P = .049). However, the Cox multivariate analysis did not demonstrate the prognostic significance of TLS.
CONCLUSIONS: TLS is heterogeneous in UCB, and that TLS and GC structures are related to TIL density and prognostic events. However, TLS as a prognostic indicator remains unclear, warranting further investigation.
METHODS: The study enrolled 580 patients with surgically treated UCB, including 313 non-muscle invasive bladder cancer (NMIBC) and 267 muscle-invasive bladder cancer (MIBC). The presence and subtypes of TLSs were identified by immunohistochemistry (CD20, CD3, Bcl-6, and CD21). TLSs were classified into non-GC (nGC) TLS and GC TLS subtypes based on germinal center (GC) formation. Disease-free survival (DFS) was used as an endpoint outcome to evaluate the prognostic significance of TLS and its subtypes in UCB.
RESULTS: TLSs were more common in MIBC than in NMIBC (67.8% vs 48.2%, P < .001), and the tumor-infiltrating lymphocyte (TIL) mean density was significantly higher in MIBC than in NMIBC (24.0% vs 17.5%, P < .001). Moreover, a positive correlation was found between TLS presence and GC structure formation and TIL infiltration in UCB. Endpoint events occurred in 191 patients. Compared to patients with endpoint events, patients without disease progression exhibited higher TIL density and more TLSs (P < .05). Kaplan-Meier curves showed that TLS was associated with better DFS in NMIBC (P = .041) and MIBC (P = .049). However, the Cox multivariate analysis did not demonstrate the prognostic significance of TLS.
CONCLUSIONS: TLS is heterogeneous in UCB, and that TLS and GC structures are related to TIL density and prognostic events. However, TLS as a prognostic indicator remains unclear, warranting further investigation.
摘要：
目的：评估膀胱尿路上皮癌（UCB）中三级淋巴结构（TLSs）的存在和亚型，并分析其相关的临床病理特征和预后意义。
方法：该研究纳入了580例接受手术治疗的UCB患者，包括313例非肌层浸润性膀胱癌（NMIBC）和267例肌层浸润性膀胱癌（MIBC）。通过免疫组织化学鉴定TLS的存在和亚型(CD20、CD3、Bcl-6和CD21)。根据生发中心（GC）的形成，将TLS分为非GC（nGC）TLS和GCTLS亚型。无病生存期（DFS）被用作终点结果，以评估TLS及其亚型在UCB中的预后意义。
结果：TLS在MIBC中比在NMIBC中更常见（67.8％vs48.2％，P<.001),MIBC的肿瘤浸润淋巴细胞（TIL）平均密度明显高于NMIBC（24.0%vs17.5%，P<.001)。此外，在UCB中，TLS的存在与GC结构形成和TIL浸润之间存在正相关。191例患者发生终点事件。与有终点事件的患者相比，无疾病进展的患者表现出更高的TIL密度和更多的TLS（P<0.05）。Kaplan-Meier曲线显示TLS与NMIBC(P=0.041)和MIBC(P=0.049)中更好的DFS相关。然而,Cox多变量分析未显示TLS的预后意义.
结论：TLS在UCB中是异构的，TLS和GC结构与TIL密度和预后事件有关。然而,TLS作为预后指标尚不清楚，保证进一步调查。
方法：该研究纳入了580例接受手术治疗的UCB患者，包括313例非肌层浸润性膀胱癌（NMIBC）和267例肌层浸润性膀胱癌（MIBC）。通过免疫组织化学鉴定TLS的存在和亚型(CD20、CD3、Bcl-6和CD21)。根据生发中心（GC）的形成，将TLS分为非GC（nGC）TLS和GCTLS亚型。无病生存期（DFS）被用作终点结果，以评估TLS及其亚型在UCB中的预后意义。
结果：TLS在MIBC中比在NMIBC中更常见（67.8％vs48.2％，P<.001),MIBC的肿瘤浸润淋巴细胞（TIL）平均密度明显高于NMIBC（24.0%vs17.5%，P<.001)。此外，在UCB中，TLS的存在与GC结构形成和TIL浸润之间存在正相关。191例患者发生终点事件。与有终点事件的患者相比，无疾病进展的患者表现出更高的TIL密度和更多的TLS（P<0.05）。Kaplan-Meier曲线显示TLS与NMIBC(P=0.041)和MIBC(P=0.049)中更好的DFS相关。然而,Cox多变量分析未显示TLS的预后意义.
结论：TLS在UCB中是异构的，TLS和GC结构与TIL密度和预后事件有关。然而,TLS作为预后指标尚不清楚，保证进一步调查。
