食管鳞状细胞癌中Trop2、Nectin-4和PD-L1的表达谱：联合免疫治疗和ADC靶向治疗的意义

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2025-05-20 DOI:10.1016/j.prp.2025.156032

Zhiyuan Yao , Ge Wei , Peng Song , Changlei Li , Guohua Wang , Zengjin Wen , Lisai Liu , Guangqi Li

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引用次数: 0

摘要

AimTrop2、Nectin-4和PD-L1分别是抗体-药物偶联（antibody-drug conjugate， ADC）药物和免疫制剂的靶标，与恶性肿瘤的生物学特性密切相关。本研究分析了Trop2、Nectin-4和PD-L1的表达及其与食管鳞状细胞癌（ESCC）的关系。方法回顾性分析青岛大学附属医院140例ESCC根治术患者的临床病理资料。采用免疫组化（IHC）方法检测标本中Trop2、Nectin-4、PD-L1的表达情况，并用组织化学评分（H-score）对表达水平进行量化和分类。对于PD-L1，还评估了联合阳性评分（CPS）。结果Trop2、Nectin-4和PD-L1的阳性率分别为99.3% %、95.7% %和43.6% %。Trop2与淋巴管侵袭、淋巴结侵袭、肿瘤分期相关，Nectin-4与淋巴管侵袭、周围神经侵袭、淋巴结侵袭、病理性T分期相关。此外，与pd - l1阴性患者相比，pd - l1阳性患者表现出更高的Trop2和Nectin-4表达升高率，淋巴管侵袭增加，病理T期晚期。此外，在可能适合免疫治疗的个体中（PD-L1 CPS >10）， PD-L1表达与Nectin-4表达呈显著弱相关性。此外，Trop2可作为ESCC患者预后不良的独立指标。结论Trop2、Nectin-4和PD-L1在ESCC中的表达情况表明免疫治疗联合ADC药物靶向治疗是可行的。

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Trop2, Nectin-4, and PD-L1 expression profiles in esophageal squamous cell carcinoma: Implications for combined immunotherapy and ADC targeted therapies

Aim

Trop2, Nectin-4, and PD-L1 are targets of antibody-drug conjugate (ADC) drugs and immunological agents, respectively, closely related to the biological characteristics of malignant tumors. This study analyzed the expression and clinical significance of Trop2, Nectin-4, and PD-L1 and their association with esophageal squamous cell carcinoma (ESCC).

Methods

Clinicopathological data of 140 patients with ESCC undergoing radical resection at the Affiliated Hospital of Qingdao University were retrospectively collected. Immunohistochemistry (IHC) was conducted to assess the expression of Trop2, Nectin-4, and PD-L1 in the specimens, with quantification and categorization of expression levels by the histochemistry score (H-score). For PD-L1, the combined positive score (CPS) was also evaluated.

Results

Positivity rates for Trop2, Nectin-4, and PD-L1 were 99.3 %, 95.7 %, and 43.6 %, respectively. Trop2 correlated with lymphatic vessel invasion, lymph node invasion, and advanced tumor stage, while Nectin-4 was associated with lymphatic vessel invasion, peripheral nerve invasion, lymph node invasion, and advanced pathological T stage. Additionally, PD-L1-positive patients exhibited higher rates of elevated Trop2 and Nectin-4 expression, increased lymphatic vessel invasion, and advanced pathological T stage compared to PD-L1-negative patients. Furthermore, among individuals potentially eligible for immunotherapy (PD-L1 CPS >10), PD-L1 expression displayed a significantly weak correlation with Nectin-4 expression. Furthermore, Trop2 served as an independent poor prognostic indicator for ESCC patients.

Conclusions

The expression landscape of Trop2, Nectin-4, and PD-L1 in ESCC indicated the feasibility of combining immunotherapy with ADC drug-targeted therapies.

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来源期刊

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.