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Publications

Journal Article Ahead of print 2 citations

PubMed: 40946743 DOI: 10.1016/j.modpat.2025.100889

Comprehensive Molecular Profiling of Cribriform Tumors: Identification of Recurrent 6q/9q Codeletion and CD38 Expression.

Mod Pathol

Authors: Pierre Sohier, Maxime Battistella, Maxime Mouthon, Arnaud de la Fouchardière, Nicolas Ortonne, Rémi Vergara, Joanna Cyrta, Audrey Gros, Elodie Laharanne, Eduardo Calonje, Sarah Menguy, Laurence Lamant, Andreas von Deimling, Franck Tirode, Daniel Pissaloux, Bernard Cribier, Thibault Kervarrec, Nicolas Macagno

Affiliations

  • CARADERM, French Network of rare skin cancers, Lille, France; Department of Pathology, Hôpital Cochin, AP-HP.Centre-Université Paris Cité, Paris, France.
  • CARADERM, French Network of rare skin cancers, Lille, France; Department of Pathology, APHP Hôpital Saint-Louis, INSERM U1342, Université Paris Cité, Paris, France.
  • CARADERM, French Network of rare skin cancers, Lille, France; Department of Biopathology, Centre Léon Bérard, Lyon, France; Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.
  • CARADERM, French Network of rare skin cancers, Lille, France; Department of Pathology, Assistance Publique - Hôpitaux de Paris (AP-HP), Henri Mondor hospital, Créteil, France; Paris est Créteil University (UPEC) and INSERM U955 (Team Ortonne), 8 rue du Général Sarrail, 94010, Créteil, France.
  • CARADERM, French Network of rare skin cancers, Lille, France; Department of Pathology, University Hospital of Bordeaux, Bordeaux, France.
  • Department of Pathology, Institut Curie, PSL Research University, Paris, France.
  • Department of Molecular Pathology, Bordeaux University Hospital - Haut Lévêque, Avenue de Haut Lévêque, 33600 Pessac, France.
  • Department of Dermatopathology, St John's institute of Dermatology, Guy's and St Thomas' NHS trust, London, United Kingdom.
  • Laboratoire Aquipath Centre de Dermatopathologie Aquitain, Talence, France.
  • CARADERM, French Network of rare skin cancers, Lille, France; Department of Pathology, Oncopole, Toulouse, France.
  • Clinical Cooperation Unit Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Department of Biopathology, Centre Léon Bérard, Lyon, France; Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France.
  • CARADERM, French Network of rare skin cancers, Lille, France; Department of Dermatology, University of Strasbourg, Strasbourg, France.
  • CARADERM, French Network of rare skin cancers, Lille, France; Department of Pathology, Université de Tours, Centre Hospitalier Universitaire de Tours, Tours, France; "Biologie des infections à polyomavirus" team, UMR INRA ISP 1282, Université de Tours, Tours, France.
  • CARADERM, French Network of rare skin cancers, Lille, France; Department of Pathology, APHM, Timone, Marseille, France; Aix Marseille Univ, INSERM, MMG, Marseille, France.

Abstract

Cribriform tumor is a distinctive cutaneous adnexal tumor with a cribriform growth pattern. Initially described as carcinomas, cribriform tumors exhibit an indolent clinical course. In contrast to many other adnexal skin neoplasms, the oncogenic driver of cribriform tumors is still unknown. This study aims to provide a novel characterization of cribriform tumors, focusing on the molecular and gene expression profiles revealed by whole transcriptome analysis using RNA sequencing and DNA methylation analysis, and describe the resulting novel genetic and protein biomarkers. The study analyzed 15 cases of cribriform tumors, including five female patients. The median age at diagnosis was 62 years (range: 37-86 years). The most common tumor locations were lower (n = 10) and upper extremities (n = 5). Histopathological analysis revealed that all tumors were dermally located, with subcutaneous extension in 11 cases. All cases exhibited a combination of trabecular, cystic, and cribriform growth patterns. Unsupervised clustering based on DNA methylation and transcriptomic profiles confirmed cribriform tumors as a strikingly homogeneous molecular entity, molecularly distinct from other adnexal neoplasms. The low-risk G2/M and CINSARC transcriptomic signatures detected in all tested cases further supported the indolent nature of this neoplasm. Copy number variation analysis derived from DNA methylation analysis revealed recurrent 6q/9q codeletion in 7/8 tested cases. This codeletion was confirmed by FISH targeting the 6q and 9q loci in 6 cases tested. RNA sequencing data did not reveal any recurrent specific fusions or specific pathogenic variants. Gene expression analysis focusing on differentially expressed genes between cribriform tumors and other cutaneous tumors revealed overexpression of CD38 in all cribriform tumors. Consistent with these findings, immunohistochemical analysis demonstrated CD38 expression in all cribriform tumors but not in controls (n=29). In conclusion, our findings support that cribriform tumors represent a homogeneous group of cutaneous adnexal neoplasms characterized by recurrent 6q/9q co-deletions and CD38 expression.

MeSH

Genes, Growth, Neoplasms, Pathology