Myriam Kossaï1, Camélia Radulescu2, Julien Adam3, Anaïs Dziegielewski2, Nicolas Signolle4, Mathilde Sibony5, Thierry Lebret6, Yves Allory7, Mathieu Rouanne8. 1. 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. Electronic address: myriamkossai@gmail.com. 2. Department of Pathology, Hôpital Foch, UVSQ-Université Paris-Saclay, Suresnes, France. 3. Department of Pathology, Hôpital Paris Saint-Joseph, Paris; INSERM U1186, Gustave Roussy, Université Paris-Saclay, Villejuif, France. 4. INSERM U981, Gustave Roussy, Université Paris-Saclay, Villejuif, France. 5. Department of Pathology, Hôpital Cochin, Université Paris-Descartes, Paris, France. 6. Department of Urology, Hôpital Foch, UVSQ-Université Paris-Saclay, Suresnes, France. 7. 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. 8. Department of Urology, Hôpital Foch, UVSQ-Université Paris-Saclay, Suresnes, France; INSERM U1015, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
Abstract
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.
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.