Article type: Research Article
Authors: Melloul, S.a | Mosnier, J.-F.b | Masliah-Planchon, J.c; d; e | Lepage, C.f; g | Le Malicot, K.g; h | Gornet, J.-M.i | Edeline, J.j | Dansette, D.b | Texereau, P.k | Delattre, O.c; d; e | Laurent Puig, P.l; m | Taieb, J.l; m | Emile, J.-F.a; n; *
Affiliations: [a] Department of Pathology, Ambroise Paré Hospital, APHP, Boulogne, France | [b] Department of Pathology, Hotel Dieu, Nantes, France | [c] Somatic Genetic Unit, Institut Curie, Paris, France | [d] Paris-Sciences-Lettres, Institut Curie Research Center, INSERMU830, Paris, France | [e] SIREDO, Institut Curie, Paris, France | [f] François Mitterrand University Hospital, Dijon, France | [g] EPICAD INSERM LNC-UMR 1231, University of Burgundy and Franche-Comté, Besançon, France | [h] Francophone Society of Digestive Cancer, Dijon, France | [i] St Louis Hospital, APHP, Paris, France | [j] Eugène Marquis Center, Rennes, France | [k] Layne Hospital Center, Mont-de-Marsan, France | [l] G. Pompidou European Hospital, APHP, Paris, France | [m] INSERM UMR-S1147, Paris, France | [n] EA4340-BCOH, Versailles SQY University, Paris-Saclay University, Boulogne, France
Correspondence:
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Corresponding author: J.-F. Emile, Service de Pathologie, Hôpital Ambroise Paré, 9 Av Ch. De Gaulle, 92104 Boulogne, France. E-mail: jean-francois.emile@uvsq.fr.
Abstract: SMARCB1 is a tumor suppressor gene, which is part of SWI/SNF complex involved in transcriptional regulation. Recently, loss of SMARCB1 expression has been reported in gastrointestinal carcinomas. Our purpose was to evaluate the incidence and prognostic value of SMARCB1 loss in colon carcinoma (CC). Patients with stage III CC (n= 1695), and a second cohort of 23 patients with poorly differentiated CC were analyzed. Immunohistochemistry for SMARCB1 was performed on tissue microarrays, and cases with loss of expression were controlled on whole sections. Loss of SMARCB1 was compared with the clinico-pathological and molecular characteristics, and the prognostic value was evaluated. Loss of SMARCB1 was identified in 12 of 1695 (0.7%) patients with stage III CC. Whole section controls showed a complete loss in only one of these cases, corresponding to a medullary carcinoma. SMARCB1 loss was not associated with histological grade, tumor size nor survival. In the cohort of poorly differentiated CC, we detected 2/23 (8.7%) cases with loss of SMARCB1; one was rhabdoid while the other had medullary and mucinous histology. These 2 cases were deficient for MisMatched Repair (dMMR) and mutated for BRAF. SMARCB1 loss is rare in stage III CC, but appears more frequent in poorly differentiated CC.
Keywords: SMARCB1, colon carcinoma, BRAF V600E, mismatch repair deficiency
DOI: 10.3233/CBM-190287
Journal: Cancer Biomarkers, vol. 27, no. 3, pp. 399-406, 2020
