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Abstract：
OBJECTIVE: Expression of the programmed death-ligand 1 (PD-L1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) in medullary thyroid carcinoma (MTC) has been controversial and rarely reported.
METHODS: Surgical specimens of 190 MTC patients who had initial curative-intent surgery were collected. Immunohistochemistry of PD-L1 and TIM-3 was performed using 22C3 pharmDx (Dako, Carpinteria, CA) and anti-TIM-3 (1:500, ab241332, Abcam). Stained slides were scored using a combined positive score (CPS) with a cutoff of ≥ 1. We established correlations between PD-L1 expression, TIM-3 expression, clinicopathological, and survival data.
RESULTS: 13 cases (13/190, 6.84%) were positive for PD-L1 expression, and 42 cases (42/154, 27.27%) for TIM-3 expression. PD-L1 expression was correlated to TIM-3 expression (P = 0.002), but was not related to overall survival (OS) or progression-free survival (PFS). TIM-3 expression was correlated to perineural invasion (P = 0.040). Multivariate Cox analysis showed that lymphovascular invasion (LVI) was independently associated with OS. And tumor size, LVI, and lymph node metastases were significantly associated with PFS. Furthermore, the multivariate logistic analysis showed multifocal status, LVI, pathological T stage and lymph node metastasis were independent risk factors for biochemical recurrence/persistent disease.
CONCLUSIONS: We demonstrated that PD-L1 and TIM-3 expression were not frequent in MTC and were not associated with survival prognosis. Our results should be considered when clinical trials of PD-L1 or TIM-3 blockades are implemented.
METHODS: Surgical specimens of 190 MTC patients who had initial curative-intent surgery were collected. Immunohistochemistry of PD-L1 and TIM-3 was performed using 22C3 pharmDx (Dako, Carpinteria, CA) and anti-TIM-3 (1:500, ab241332, Abcam). Stained slides were scored using a combined positive score (CPS) with a cutoff of ≥ 1. We established correlations between PD-L1 expression, TIM-3 expression, clinicopathological, and survival data.
RESULTS: 13 cases (13/190, 6.84%) were positive for PD-L1 expression, and 42 cases (42/154, 27.27%) for TIM-3 expression. PD-L1 expression was correlated to TIM-3 expression (P = 0.002), but was not related to overall survival (OS) or progression-free survival (PFS). TIM-3 expression was correlated to perineural invasion (P = 0.040). Multivariate Cox analysis showed that lymphovascular invasion (LVI) was independently associated with OS. And tumor size, LVI, and lymph node metastases were significantly associated with PFS. Furthermore, the multivariate logistic analysis showed multifocal status, LVI, pathological T stage and lymph node metastasis were independent risk factors for biochemical recurrence/persistent disease.
CONCLUSIONS: We demonstrated that PD-L1 and TIM-3 expression were not frequent in MTC and were not associated with survival prognosis. Our results should be considered when clinical trials of PD-L1 or TIM-3 blockades are implemented.
摘要：
目的：程序性死亡配体1（PD-L1）和T细胞免疫球蛋白和含粘蛋白结构域3（TIM-3）在甲状腺髓样癌（MTC）中的表达一直存在争议，很少报道。
方法：收集190例接受初始治愈性手术的MTC患者的手术标本。使用22C3pharmDx（Dako，Carpinteria,CA）和抗TIM-3（1：500，ab241332，Abcam）。使用组合阳性评分（CPS）对染色载玻片进行评分，临界值≥1。我们建立了PD-L1表达之间的相关性，TIM-3表达式,临床病理,和生存数据。
结果：13例（13/190，6.84%）PD-L1阳性表达，42例(42/154,27.27%)为TIM-3表达。PD-L1表达与TIM-3表达相关(P=0.002),但与总生存期(OS)或无进展生存期(PFS)无关.TIM-3表达与神经周浸润相关(P=0.040)。多因素Cox分析显示，淋巴血管侵犯（LVI）与OS独立相关。还有肿瘤的大小,LVI,淋巴结转移与PFS显著相关。此外，多变量逻辑分析显示多病灶状态，LVI,病理T分期和淋巴结转移是生化复发/疾病持续的独立危险因素。
结论：我们证明PD-L1和TIM-3的表达在MTC中并不常见，并且与生存预后无关。在实施PD-L1或TIM-3阻断的临床试验时，应考虑我们的结果。
方法：收集190例接受初始治愈性手术的MTC患者的手术标本。使用22C3pharmDx（Dako，Carpinteria,CA）和抗TIM-3（1：500，ab241332，Abcam）。使用组合阳性评分（CPS）对染色载玻片进行评分，临界值≥1。我们建立了PD-L1表达之间的相关性，TIM-3表达式,临床病理,和生存数据。
结果：13例（13/190，6.84%）PD-L1阳性表达，42例(42/154,27.27%)为TIM-3表达。PD-L1表达与TIM-3表达相关(P=0.002),但与总生存期(OS)或无进展生存期(PFS)无关.TIM-3表达与神经周浸润相关(P=0.040)。多因素Cox分析显示，淋巴血管侵犯（LVI）与OS独立相关。还有肿瘤的大小,LVI,淋巴结转移与PFS显著相关。此外，多变量逻辑分析显示多病灶状态，LVI,病理T分期和淋巴结转移是生化复发/疾病持续的独立危险因素。
结论：我们证明PD-L1和TIM-3的表达在MTC中并不常见，并且与生存预后无关。在实施PD-L1或TIM-3阻断的临床试验时，应考虑我们的结果。
