Complete Loss of EPCAM Immunoexpression Identifies EPCAM Deletion Carriers in MSH2-Negative Colorectal Neoplasia
by
1,2,3
, 4, 5, 5,6, 7,8, 9, 2,10,11,12,13, 14, 13,15, 13,15, 13,15, 13,16, 17, 18, 19, 20, 3,21, 6,22, 2,13,23,24 and 14,22,23,*
, 4, 5, 5,6, 7,8, 9, 2,10,11,12,13, 14, 13,15, 13,15, 13,15, 13,16, 17, 18, 19, 20, 3,21, 6,22, 2,13,23,24 and 14,22,23,*
1
Department of Pathology, Center of Biomedical Diagnosis (CDB), Hospital Clínic, 08036 Barcelona, Spain
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Universitat de Barcelona (UB), 08007 Barcelona, Spain
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Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 08036 Barcelona, Spain
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Department of Pathology, Hospital Universitario de Araba, 01009 Vitoria-Gasteiz, Spain
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Gastroenterology Department, Hospital Universitari General de Catalunya-Grupo Quirónsalud, Sant Cugat del Valles, 08195 Barcelona, Spain
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Universitat Internacional de Catalunya (UIC), Sant Cugat del Vallès, 08017 Barcelona, Spain
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Oncology Department, Parc Taulí Hospital Universitari, Sabadell, 08208 Barcelona, Spain
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Oncology Department, Consorci Sanitari de Terrassa, Terrassa, 08208 Barcelona, Spain
9
Department of Pathology, Parc Taulí Hospital Universitari, Sabadell, 08208 Barcelona, Spain
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Department of Pathology, Hospital Universitari de Bellvitge, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), L’Hospitalet de Llobregat, 08908 Barcelona, Spain
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Department of Pathology, Hospital Universitari Arnau de Vilanova, 25198 Lleida, Spain
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Universitat de Lleida, IRBLLEIDA, 25003 Lleida, Catalonia, Spain
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Centro de Investigación Biomédica en Red Cancer (CIBERONC), 28029 Madrid, Spain
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Department of Pathology, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Barcelona, Spain
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Hereditary Cancer Program, Catalan Institute of Oncology, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), ONCOBELL Program, Hospitalet de Llobregat, 08908 Barcelona, Spain
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Hereditary Cancer Program, Catalan Institute of Oncology, Institut d’Investigació Biomèdica de Girona (IDIBGI), Universitat de Girona, 17190 Girona, Spain
17
Department of Pathology, Hospital Quirónsalud Barcelona, 08023 Barcelona, Spain
18
Department of Pathology, Hospital Platón, 08006 Barcelona, Spain
19
Department of Pathology, Hospital Universitario Príncipe de Asturias, 28805 Alcalá de Henares, Madrid, Spain
20
Department of Pathology, University Hospital Josep Trueta, 17007 Girona, Spain
21
Gastroenterology Department, Institut de Malalties Digestives i Metabòliques, Hospital Clínic, 08036 Barcelona, Spain
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Department of Pathology, Hospital Universitari General de Catalunya-Grupo Quirónsalud, Sant Cugat del Vallès, 08190 Barcelona, Spain
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Josep Carreras Leukaemia Research Institute (IJC), 08916 Badalona, Barcelona, Spain
24
Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(10), 2803; https://doi.org/10.3390/cancers12102803
Received: 25 July 2020
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Revised: 23 September 2020
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Accepted: 26 September 2020
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Published: 29 September 2020
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
Simple Summary
Colorectal carcinomas from patients with Lynch syndrome (LS) due to EPCAM deletions show loss of MSH2 expression. The aim of our study was to evaluate the usefulness of EPCAM expression in identifying carriers of EPCAM deletion among patients with MSH2-negative lesions. MSH2 and EPCAM immunohistochemistry was performed in a large series of lesions (190) composed of malignant and benign neoplasms as well as precursor lesions of different organs from 71 patients with suspected LS due to MSH2 alterations. Germ-line analysis confirmed LS in 68 patients due to MSH2 mutations (53) and EPCAM deletions (15). Among colorectal lesions with lack of MSH2 expression, only 17 were EPCAM-negative and belonged to patients with EPCAM deletions. We confirm that loss of EPCAM expression identifies EPCAM deletion carriers with 100% specificity and we recommend adding EPCAM IHC to the algorithm of MSH2-negative colorectal neoplasia.
The use of epithelial cell adhesion molecule (EPCAM) immunohistochemistry (IHC) is not included in the colorectal cancer (CRC) screening algorithm to detect Lynch syndrome (LS) patients. The aim of the present study was to demonstrate that EPCAM IHC is a useful tool to guide the LS germ-line analysis when a loss of MSH2 expression was present. We retrospectively studied MSH2 and EPCAM IHC in a large series of 190 lesions composed of malignant neoplasms (102), precursor lesions of gastrointestinal (71) and extra-gastrointestinal origin (9), and benign neoplasms (8) from different organs of 71 patients suspicious of being LS due to MSH2 alterations. LS was confirmed in 68 patients, 53 with MSH2 mutations and 15 with EPCAM 3′-end deletions. Tissue microarrays were constructed with human normal tissues and their malignant counterparts to assist in the evaluation of EPCAM staining. Among 154 MSH2-negative lesions, 17 were EPCAM-negative, including 10 CRC and 7 colorectal polyps, and 5 of them showed only isolated negative glands. All lesions showing a lack of EPCAM expression belonged to patients with EPCAM 3′-end deletions. EPCAM IHC is a useful screening tool, with 100% specificity to identify LS patients due to EPCAM 3′-end deletions in MSH2-negative CRC and MSH2-negative colorectal polyps.
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Keywords:
lynch syndrome; EPCAM; immunohistochemistry; colorectal cancer; colon polyps
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MDPI and ACS Style
Cuatrecasas, M.; Gorostiaga, I.; Riera, C.; Saperas, E.; Llort, G.; Costa, I.; Matias-Guiu, X.; Carrato, C.; Navarro, M.; Pineda, M.; Dueñas, N.; Brunet, J.; Marco, V.; Trias, I.; Busteros, J.I.; Mateu, G.; Balaguer, F.; Fernández-Figueras, M.-T.; Esteller, M.; Musulén, E. Complete Loss of EPCAM Immunoexpression Identifies EPCAM Deletion Carriers in MSH2-Negative Colorectal Neoplasia. Cancers 2020, 12, 2803. https://doi.org/10.3390/cancers12102803
AMA Style
Cuatrecasas M, Gorostiaga I, Riera C, Saperas E, Llort G, Costa I, Matias-Guiu X, Carrato C, Navarro M, Pineda M, Dueñas N, Brunet J, Marco V, Trias I, Busteros JI, Mateu G, Balaguer F, Fernández-Figueras M-T, Esteller M, Musulén E. Complete Loss of EPCAM Immunoexpression Identifies EPCAM Deletion Carriers in MSH2-Negative Colorectal Neoplasia. Cancers. 2020; 12(10):2803. https://doi.org/10.3390/cancers12102803
Chicago/Turabian StyleCuatrecasas, Míriam, Iñigo Gorostiaga, Cristina Riera, Esteban Saperas, Gemma Llort, Irmgard Costa, Xavier Matias-Guiu, Cristina Carrato, Matilde Navarro, Marta Pineda, Núria Dueñas, Joan Brunet, Vicente Marco, Isabel Trias, José I. Busteros, Gemma Mateu, Francesc Balaguer, María-Teresa Fernández-Figueras, Manel Esteller, and Eva Musulén. 2020. "Complete Loss of EPCAM Immunoexpression Identifies EPCAM Deletion Carriers in MSH2-Negative Colorectal Neoplasia" Cancers 12, no. 10: 2803. https://doi.org/10.3390/cancers12102803
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