Plasmacytoid urothelial carcinoma (UC) are luminal tumors with similar CD8+ Tcell density and PD-L1 protein expression on immune cells as compared to conventional UC,Urologic Oncology: Seminars and Original Investigations

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Plasmacytoid urothelial carcinoma (UC) are luminal tumors with similar CD8+ Tcell density and PD-L1 protein expression on immune cells as compared to conventional UC
Urologic Oncology: Seminars and Original Investigations ( IF 2.7 ) Pub Date : 2021-08-21 , DOI: 10.1016/j.urolonc.2021.07.014
Myriam Kossaï ₁ , Camélia Radulescu ₂ , Julien Adam ₃ , Anaïs Dziegielewski ₂ , Nicolas Signolle ₄ , Mathilde Sibony ₅ , Thierry Lebret ₆ , Yves Allory ₇ , Mathieu Rouanne ₈

Affiliation

Department of Pathology, Hôpital Foch, UVSQ-Université Paris-Saclay, Suresnes, France; Department of Pathology and Molecular Biology, Centre Jean Perrin, Clermont-Ferrand, France; National Institute of Health and Medical Research (INSERM) 1240, Université Clermont Auvergne, Clermont-Ferrand, France.
Department of Pathology, Hôpital Foch, UVSQ-Université Paris-Saclay, Suresnes, France.
Department of Pathology, Hôpital Paris Saint-Joseph, Paris; INSERM U1186, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
INSERM U981, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
Department of Pathology, Hôpital Cochin, Université Paris-Descartes, Paris, France.
Department of Urology, Hôpital Foch, UVSQ-Université Paris-Saclay, Suresnes, France.
Department of Pathology, Institut Curie, Saint-Cloud, France; Centre National de la Recherche Scientifique (CNRS) UMR144, Equipe Labellisée Ligue Nationale Contre le Cancer, Paris, France.
Department of Urology, Hôpital Foch, UVSQ-Université Paris-Saclay, Suresnes, France; INSERM U1015, Gustave Roussy, Université Paris-Saclay, Villejuif, France.

Background

Plasmacytoid urothelial carcinoma (UC) is a rare pathological variant of UC with low chemotherapeutic sensitivity and dismal outcomes. The molecular and immune profiles of such tumors remain poorly investigated.

Methods

Herein, we investigated the phenotypical features of a cohort of plasmacytoid UC (n=32) by comparison to a control group of conventional high-grade UC with matched clinicopathological characteristics (n=30). Histopathological analysis included the following antibodies: p63, GATA3, CK5/6, CK20 and HER2. In addition, the density of intra-tumor CD8⁺ lymphocytes, and PD-L1 expression in tumor (TC) and immune cells (IC) were evaluated.

Results

Plasmacytoid UC expressed GATA3 (97% vs 86% P=0.18), CK20 (59% vs 36% P=0.08) markers and showed a significantly higher rate of HER2 overexpression (2+ and 3+ score: 25% vs 0%, P<0.01) compared to controls. A significantly lower expression of CK5/6 (22% vs 56%, P<0.05) and p63 (41% vs 80%, P<0.05) was observed in plasmacytoid UC compared to controls. The density of tumor-infiltrating CD8+ cells was similar between plasmacytoid and conventional UC (P=0.9). PD-L1 expression on IC was similar compared to conventional UC (P=0.3).

Conclusions

Together, our study demonstrated that plasmacytoid UC belong to the luminal subtype and display a rather inflamed microenvironment similar to conventional UC. These data support the inclusion of plasmacytoid variant of UC in clinical trials evaluating immune checkpoint inhibitors monotherapy or combination immunotherapeutic strategies.

中文翻译：

浆细胞样尿路上皮癌 (UC) 是腔内肿瘤，与常规 UC 相比，免疫细胞上的 CD8+ T 细胞密度和 PD-L1 蛋白表达相似

背景

浆细胞样尿路上皮癌 (UC) 是一种罕见的 UC 病理变体，具有低化疗敏感性和令人沮丧的结果。这种肿瘤的分子和免疫特征仍然很少被研究。

方法

在这里，我们通过与具有匹配临床病理学特征（ n = 30）的常规高级 UC 对照组进行比较，研究了一组浆细胞样 UC（n = 32）的表型特征。组织病理学分析包括以下抗体：p63、GATA3、CK5/6、CK20 和 HER2。此外，还评估了肿瘤内 CD8 ⁺淋巴细胞的密度，以及肿瘤 (TC) 和免疫细胞 (IC) 中 PD-L1 的表达。

结果

浆细胞样 UC 表达 GATA3 (97% vs 86% P =0.18)、CK20 (59% vs 36% P =0.08) 标志物并显示出显着更高的 HER2 过表达率（2+ 和 3+ 评分：25% vs 0%，P <0.01）与对照相比。与对照组相比，在浆细胞样 UC 中观察到CK5/6（22% 对 56%，P <0.05）和 p63（41% 对 80%，P <0.05）的表达显着降低。浆细胞样和常规 UC 的肿瘤浸润 CD8+ 细胞密度相似（P = 0.9）。与常规 UC 相比，IC 上的 PD-L1 表达相似（P = 0.3）。