Primary glandular bladder tumours (bladder adenocarcinoma [BAC], urachal adenocarcinoma [UAC], urothelial carcinoma with glandular differentiation [UCg]) are rare malignancies with histological resemblance to colorectal adenocarcinoma (CORAD) in the majority of this subgroup. Definite case numbers are very low, molecular data are limited and the pathogenesis remains poorly understood. Therefore, this study was designed to complement current knowledge by in depth analysis of BAC (n = 12), UAC (n = 13), UCg (n = 11) and non-invasive glandular lesions (n = 19). In BAC, in addition to known alterations in TP53, Wnt, MAP kinase and MTOR pathway, mutations in SMAD4, ARID1A and BRAF were identified. Compared to published data on muscle invasive bladder cancer (BLCA) and CORAD, UCg exhibited frequent "urothelial" like alterations while BAC and UAC were characterised by a more "colorectal" like mutational pattern. Immunohistochemically, there was no evidence of DNA mismatch repair deficiency or PD-L1 tumour cell positivity in any sample. Depending on the used antibody 0-45% of BAC, 0-30% of UCg and 0% UAC cases exhibited PD-L1 expressing tumour associated immune cells. A single BAC (9%, 1/11) showed evidence of ARID1A protein loss, and two cases of UCg (20%, 2/10) showed loss of SMARCA1 and PBRM1, respectively. Taken together, our data suggest at least in part involvement of similar pathways driving tumourigenesis of adenocarcinomas like BAC, UAC and CORAD independent of their tissue origin. Alterations of TERT and FBXW7 in single cases of intestinal metaplasia further point towards a possible precancerous character in line with previous reports.
Virchows Archiv : an international journal of pathology. 2020 Mar 20 [Epub ahead of print]
Angela Maurer, Nadina Ortiz-Bruechle, Karolina Guricova, Michael Rose, Ronja Morsch, Stefan Garczyk, Robert Stöhr, Simone Bertz, Reinhard Golz, Henning Reis, Felix Bremmer, Annette Zimpfer, Sabine Siegert, Glen Kristiansen, Kristina Schwamborn, Nikolaus Gassler, Ruth Knuechel, Nadine T Gaisa, German study group of bladder cancer
Institute of Pathology, University Hospital RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany., Institute of Pathology, University Hospital Erlangen, Erlangen, Germany., Institute of Pathology, HELIOS Clinic Wuppertal, Wuppertal, Germany., Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Institute of Pathology, University Medical Center, University of Göttingen, Göttingen, Germany., Institute of Pathology, University Medical Center Rostock, Rostock, Germany., Institute of Pathology Munich-North, Munich, Germany., Institute of Pathology, University Hospital Bonn, Bonn, Germany., Institute of Pathology, Technical University Munich, Munich, Germany., Institute of Legal Medicine, Section Pathology, University Hospital Jena, Jena, Germany., Institute of Pathology, University Hospital RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany. .