Immunohistochemical expression of Nectin-4 and potential implications for enfortumab vedotin therapy in germ cell tumors of the testis: a preliminary study.

IF 3.1 3区 医学 Q1 PATHOLOGY
Costantino Ricci, Francesca Ambrosi, Tania Franceschini, Alessia Grillini, Eugenia Franchini, Francesco Vasuri, Agnese Orsatti, Luisa Di Sciascio, Francesco Massari, Veronica Mollica, Andrea Marchetti, Federico Mineo Bianchi, Maurizio Colecchia, Andres Martin Acosta, João Lobo, Michelangelo Fiorentino
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Abstract

A subset of germ cell tumors of the testis (GCTT) shows an aggressive clinical behavior, with chemo-resistance, metastases, and recurrences. Recently, enfortumab vedotin (EV), an antibody-drug conjugate (ADC) targeting Nectin-4, has been shown to improve the survival in urothelial carcinoma and has been approved for the locally advanced or metastatic cases. We stained for Nectin-4 (EPR15613-68 rb, Abcam) 46 cases (42 chemo-naive primary testicular tumors and 4 post-chemotherapy metastatic recurrences) and adopted the H-score and the specific Nectin-4 score (negative (H-score 0-14), weak (H-score 15-99), moderate (H-score 100-199), and strong (H-score 200-300)) for both the cytoplasm and the membrane. The expression of Nectin-4 was compared between different histotypes by adopting the specific Nectin-4 score and Fisher's exact test. Nectin-4 membrane expression was positive in 14/89 (15.7%) GCTT components, with median H-score of 0 (range 0-120; IQR 0-10). Choriocarcinoma (CHC) (median H-score 29 (range 20-40, IQR 21.25-38.25)) and isolated syncytiotrophoblast cells (iSTCs) [median H-score 65 (range 0-90; IQR 10-147.5)) showed statistically significant higher Nectin-4 membrane expression than the other GCTT components (p < 0.001), with staining mostly observed in syncytiotrophoblasts in CHC and thus mirroring what found in "normal" syncytiotrophoblasts of placental tissue (adopted as positive control). Additionally, 2/4 (50%) post-chemotherapy metastatic recurrences (one Tpt and one YSTpt) and 3/25 (12%) EC showed positive weak Nectin-4 membrane expression. To summarize, our study reveals that only a small minority of GCTT exhibit positive weak Nectin-4 membrane expression. However, a subgroup of potentially aggressive GCTT (especially CHC and post-chemotherapy metastatic recurrences) more frequently exhibits Nectin-4 membrane expression, thus prompting future studies to assess whether these patients may be potentially eligible for EV therapy.

睾丸生殖细胞肿瘤中Nectin-4的免疫组织化学表达及其对强制维多汀治疗的潜在影响:初步研究。
睾丸生殖细胞肿瘤(GCTT)的一个亚群表现出侵袭性的临床行为,具有化疗耐药、转移和复发。最近,针对Nectin-4的抗体-药物偶联物(ADC) enfortumab vedotin (EV)已被证明可以提高尿路上皮癌的生存率,并已被批准用于局部晚期或转移病例。我们对46例(42例化疗初期睾丸原发肿瘤和4例化疗后转移复发)进行了Nectin-4 (epr15613 - 68rb, Abcam)染色,并对细胞质和细胞膜分别采用h评分和特异性评分(阴性(h评分0-14)、弱(h评分15-99)、中等(h评分100-199)、强(h评分200-300))。采用特异性Nectin-4评分法和Fisher精确检验比较不同组织型间Nectin-4的表达。14/89 (15.7%) GCTT成分中Nectin-4膜表达阳性,中位h评分为0(范围0-120;IQR 0-10)。绒毛膜癌(CHC) (h -评分中位数为29(范围20-40,IQR为21.25-38.25))和分离的合胞滋养细胞(iSTCs) (h -评分中位数为65(范围0-90,IQR为10-147.5))的Nectin-4膜表达高于其他GCTT成分(p
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来源期刊
Virchows Archiv
Virchows Archiv 医学-病理学
CiteScore
7.40
自引率
2.90%
发文量
204
审稿时长
4-8 weeks
期刊介绍: Manuscripts of original studies reinforcing the evidence base of modern diagnostic pathology, using immunocytochemical, molecular and ultrastructural techniques, will be welcomed. In addition, papers on critical evaluation of diagnostic criteria but also broadsheets and guidelines with a solid evidence base will be considered. Consideration will also be given to reports of work in other fields relevant to the understanding of human pathology as well as manuscripts on the application of new methods and techniques in pathology. Submission of purely experimental articles is discouraged but manuscripts on experimental work applicable to diagnostic pathology are welcomed. Biomarker studies are welcomed but need to abide by strict rules (e.g. REMARK) of adequate sample size and relevant marker choice. Single marker studies on limited patient series without validated application will as a rule not be considered. Case reports will only be considered when they provide substantial new information with an impact on understanding disease or diagnostic practice.
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