PD-L1在HPV相关性外阴阴道鳞状细胞癌和HPV非相关性外阴阴道鳞状细胞癌中的表达。

IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY International Journal of Gynecological Pathology Pub Date : 2024-07-01 Epub Date: 2024-02-02 DOI:10.1097/PGP.0000000000001003
Chau Minh Bui, Fabiola Medeiros, Mahzad Azimpouran, Mariza Venturina, Bonnie Balzer
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引用次数: 0

摘要

外阴鳞状细胞癌(VSCC)的发病机制涉及两种病因途径:一种是高危人乳头瘤病毒(HPV)相关途径,另一种是以TP53突变为特征的HPV无关途径。程序性细胞死亡配体1(PD-L1)在预测不同解剖部位的鳞状细胞癌对检查点抑制剂疗法的反应方面越来越有用。本研究旨在评估PD-L1表达与VSCC亚型之间的关联,以评估PD-L1在预后和基于HPV状态的治疗选择中的作用。PD-L1状态采用3种不同的指标来评估PD-L1在不同细胞类型中的染色程度:免疫细胞评分、肿瘤比例评分(TPS)和综合阳性评分。研究组包括25个HPV相关性VSCC和28个HPV非相关性VSCC。根据所有三种评分标准,大多数VSCC的PD-L1表达均为阳性(免疫细胞评分为84.9%,TPS评分为77.3%,综合阳性评分为90.6%)。两组中的大多数病例都观察到了 PD-L1 表达(60%-96.4%)。采用TPS法的PD-L1表达在HPV独立肿瘤中高于HPV相关肿瘤(P = 0.004),PD-L1高表达在HPV独立亚型中也更为常见(采用TPS法的P = 0.016,采用联合阳性评分法的P = 0.013)。越来越多的证据表明,PD-L1在大多数侵袭性VSCC中都有表达,因此可能成为一个有吸引力的治疗靶点。PD-L1在HPV依赖性肿瘤中的表达量更高,这表明该亚型可能对PD-L1抑制剂治疗反应更强。
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PD-L1 Expression in HPV-associated Versus HPV-independent Invasive Vulvar Squamous Cell Carcinoma.

Two etiological pathways have been implicated in the pathogenesis of vulvar squamous cell carcinoma (VSCC): a high-risk human papillomavirus (HPV)-associated route and an HPV-independent pathway characterized by TP53 mutations. Programmed cell death ligand 1 (PD-L1) has become increasingly useful in predicting the response to checkpoint inhibitor therapy in squamous cell carcinomas at various anatomical sites. This study aimed to assess the association between PD-L1 expression and the VSCC subtype to evaluate the utility of PD-L1 in prognostication and therapeutic selection based on HPV status. PD-L1 status was assessed using 3 separate metrics for the extent of PD-L1 staining in various cell types: immune cell score, tumor proportion score (TPS), and combined positive score. The study group consisted of 25 HPV-associated and 28 HPV-independent VSCCs. PD-L1 expression was positive in the majority of VSCCs according to all 3 scoring metrics (84.9% by immune cell score, 77.3% by TPS, and 90.6% by combined positive score). PD-L1 expression was observed in the majority of cases in both groups (60%-96.4%). PD-L1 expression using the TPS method was greater in HPV-independent tumors than in HPV-associated tumors ( P = 0.004), and high PD-L1 expression was also more common in the HPV-independent subtype ( P = 0.016 using the TPS method and P = 0.013 using the combined positive score method). Our findings contribute to the growing evidence that PD-L1 is expressed in the majority of invasive VSCCs, and thus may serve as an attractive therapeutic target. PD-L1 expression is higher in HPV-independent tumors, suggesting that this subtype may be more responsive to PD-L1 inhibitor therapy.

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来源期刊
CiteScore
3.90
自引率
12.50%
发文量
154
审稿时长
6-12 weeks
期刊介绍: International Journal of Gynecological Pathology is the official journal of the International Society of Gynecological Pathologists (ISGyP), and provides complete and timely coverage of advances in the understanding and management of gynecological disease. Emphasis is placed on investigations in the field of anatomic pathology. Articles devoted to experimental or animal pathology clearly relevant to an understanding of human disease are published, as are pathological and clinicopathological studies and individual case reports that offer new insights.
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