{"entity": "journal", "iuid": "0d5bfb8a2d8c4d2d939e074fa1ade50a", "timestamp": "2026-08-19T20:58:15.589Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Lancet%20Oncol.json"}, "display": {"href": "https://publications.scilifelab.se/journal/Lancet%20Oncol"}}, "title": "Lancet Oncol", "issn": "1474-5488", "issn-l": null, "publications_count": 2, "publications": [{"entity": "publication", "iuid": "a39aa8cb362d4d9c825eaa724c884d0f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a39aa8cb362d4d9c825eaa724c884d0f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a39aa8cb362d4d9c825eaa724c884d0f"}}, "title": "Genotype-first approach to identify associations between CDH1 germline variants and cancer phenotypes: a multicentre study by the European Reference Network on Genetic Tumour Risk Syndromes.", "authors": [{"family": "Garcia-Pelaez", "given": "Jos\u00e9", "initials": "J"}, {"family": "Barbosa-Matos", "given": "Rita", "initials": "R"}, {"family": "Lobo", "given": "Silvana", "initials": "S"}, {"family": "Dias", "given": "Alexandre", "initials": "A"}, {"family": "Garrido", "given": "Luzia", "initials": "L"}, {"family": "Castedo", "given": "S\u00e9rgio", "initials": "S"}, {"family": "Sousa", "given": "S\u00f3nia", "initials": "S"}, {"family": "Pinheiro", "given": "Hugo", "initials": "H"}, {"family": "Sousa", "given": "Liliana", "initials": "L"}, {"family": "Monteiro", "given": "Rita", "initials": "R"}, {"family": "Maqueda", "given": "Joaquin J", "initials": "JJ"}, {"family": "Fernandes", "given": "Susana", "initials": "S"}, {"family": "Carneiro", "given": "F\u00e1tima", "initials": "F"}, {"family": "Pinto", "given": "N\u00e1dia", "initials": "N"}, {"family": "Lemos", "given": "Carolina", "initials": "C"}, {"family": "Pinto", "given": "Carla", "initials": "C"}, {"family": "Teixeira", "given": "Manuel R", "initials": "MR"}, {"family": "Aretz", "given": "Stefan", "initials": "S"}, {"family": "Bajalica-Lagercrantz", "given": "Svetlana", "initials": "S"}, {"family": "Balma\u00f1a", "given": "Judith", "initials": "J"}, {"family": "Blatnik", "given": "Ana", "initials": "A"}, {"family": "Benusiglio", "given": "Patrick R", "initials": "PR"}, {"family": "Blanluet", "given": "Maud", "initials": "M"}, {"family": "Bours", "given": "Vincent", "initials": "V"}, {"family": "Brems", "given": "Hilde", "initials": "H"}, {"family": "Brunet", "given": "Joan", "initials": "J"}, {"family": "Calistri", "given": "Daniele", "initials": "D"}, {"family": "Capell\u00e1", "given": "Gabriel", "initials": "G"}, {"family": "Carrera", "given": "Sergio", "initials": "S"}, {"family": "Colas", "given": "Chrystelle", "initials": "C"}, {"family": "Dahan", "given": "Karin", "initials": "K"}, {"family": "de Putter", "given": "Robin", "initials": "R"}, {"family": "Desseign\u00e9s", "given": "Camille", "initials": "C"}, {"family": "Dom\u00ednguez-Garrido", "given": "Elena", "initials": "E"}, {"family": "Egas", "given": "Concei\u00e7\u00e3o", "initials": "C"}, {"family": "Evans", "given": "D Gareth", "initials": "DG"}, {"family": "Feret", "given": "Damien", "initials": "D"}, {"family": "Fewings", "given": "Eleanor", "initials": "E"}, {"family": "Fitzgerald", "given": "Rebecca C", "initials": "RC"}, {"family": "Coulet", "given": "Florence", "initials": "F"}, {"family": "Garcia-Barcina", "given": "Mar\u00eda", "initials": "M"}, {"family": "Genuardi", "given": "Maurizio", "initials": "M"}, {"family": "Golmard", "given": "Lisa", "initials": "L"}, {"family": "Hackmann", "given": "Karl", "initials": "K"}, {"family": "Hanson", "given": "Helen", "initials": "H"}, {"family": "Holinski-Feder", "given": "Elke", "initials": "E"}, {"family": "H\u00fcneburg", "given": "Robert", "initials": "R"}, {"family": "Krajc", "given": "Mateja", "initials": "M"}, {"family": "Lagerstedt-Robinson", "given": "Kristina", "initials": "K"}, {"family": "L\u00e1zaro", "given": "Conxi", "initials": "C"}, {"family": "Ligtenberg", "given": "Marjolijn J L", "initials": "MJL"}, {"family": "Mart\u00ednez-Bouzas", "given": "Cristina", "initials": "C"}, {"family": "Merino", "given": "Sonia", "initials": "S"}, {"family": "Michils", "given": "Genevi\u00e8ve", "initials": "G"}, {"family": "Novakovi\u0107", "given": "Srdjan", "initials": "S"}, {"family": "Pati\u00f1o-Garc\u00eda", "given": "Ana", "initials": "A"}, {"family": "Ranzani", "given": "Guglielmina Nadia", "initials": "GN"}, {"family": "Schr\u00f6ck", "given": "Evelin", "initials": "E"}, {"family": "Silva", "given": "In\u00eas", "initials": "I"}, {"family": "Silveira", "given": "Catarina", "initials": "C"}, {"family": "Soto", "given": "Jos\u00e9 L", "initials": "JL"}, {"family": "Spier", "given": "Isabel", "initials": "I"}, {"family": "Steinke-Lange", "given": "Verena", "initials": "V"}, {"family": "Tedaldi", "given": "Gianluca", "initials": "G"}, {"family": "Tejada", "given": "Mar\u00eda-Isabel", "initials": "MI"}, {"family": "Woodward", "given": "Emma R", "initials": "ER"}, {"family": "Tischkowitz", "given": "Marc", "initials": "M"}, {"family": "Hoogerbrugge", "given": "Nicoline", "initials": "N"}, {"family": "Oliveira", "given": "Carla", "initials": "C"}], "type": "multicenter study", "published": "2023-01-00", "journal": {"title": "Lancet Oncol", "issn": "1474-5488", "volume": "24", "issue": "1", "pages": "91-106", "issn-l": null}, "abstract": "Truncating pathogenic or likely pathogenic variants of CDH1 cause hereditary diffuse gastric cancer (HDGC), a tumour risk syndrome that predisposes carrier individuals to diffuse gastric and lobular breast cancer. Rare CDH1 missense variants are often classified as variants of unknown significance. We conducted a genotype-phenotype analysis in families carrying rare CDH1 variants, comparing cancer spectrum in carriers of pathogenic or likely pathogenic variants (PV/LPV; analysed jointly) or missense variants of unknown significance, assessing the frequency of families with lobular breast cancer among PV/LPV carrier families, and testing the performance of lobular breast cancer-expanded criteria for CDH1 testing.\n\nThis genotype-first study used retrospective diagnostic and clinical data from 854 carriers of 398 rare CDH1 variants and 1021 relatives, irrespective of HDGC clinical criteria, from 29 institutions in ten member-countries of the European Reference Network on Tumour Risk Syndromes (ERN GENTURIS). Data were collected from Oct 1, 2018, to Sept 20, 2022. Variants were classified by molecular type and clinical actionability with the American College of Medical Genetics and Association for Molecular Pathology CDH1 guidelines (version 2). Families were categorised by whether they fulfilled the 2015 and 2020 HDGC clinical criteria. Genotype-phenotype associations were analysed by Student's t test, Kruskal-Wallis, \u03c72, and multivariable logistic regression models. Performance of HDGC clinical criteria sets were assessed with an equivalence test and Youden index, and the areas under the receiver operating characteristic curves were compared by Z test.\n\nFrom 1971 phenotypes (contributed by 854 probands and 1021 relatives aged 1-93 years), 460 had gastric and breast cancer histology available. CDH1 truncating PV/LPVs occurred in 176 (21%) of 854 families and missense variants of unknown significance in 169 (20%) families. Multivariable logistic regression comparing phenotypes occurring in families carrying PV/LPVs or missense variants of unknown significance showed that lobular breast cancer had the greatest positive association with the presence of PV/LPVs (odds ratio 12\u00b739 [95% CI 2\u00b766-57\u00b774], p=0\u00b70014), followed by diffuse gastric cancer (8\u00b700 [2\u00b718-29\u00b739], p=0\u00b70017) and gastric cancer (7\u00b781 [2\u00b703-29\u00b796], p=0\u00b70027). 136 (77%) of 176 families carrying PV/LPVs fulfilled the 2015 HDGC criteria. Of the remaining 40 (23%) families, who did not fulfil the 2015 criteria, 11 fulfilled the 2020 HDGC criteria, and 18 had lobular breast cancer only or lobular breast cancer and gastric cancer, but did not meet the 2020 criteria. No specific CDH1 variant was found to predispose individuals specifically to lobular breast cancer, although 12 (7%) of 176 PV/LPV carrier families had lobular breast cancer only. Addition of three new lobular breast cancer-centred criteria improved testing sensitivity while retaining high specificity. The probability of finding CDH1 PV/LPVs in patients fulfilling the lobular breast cancer-expanded criteria, compared with the 2020 criteria, increased significantly (AUC 0\u00b792 vs 0\u00b788; Z score 3\u00b754; p=0\u00b70004).\n\nCDH1 PV/LPVs were positively associated with HDGC-related phenotypes (lobular breast cancer, diffuse gastric cancer, and gastric cancer), and no evidence for a positive association with these phenotypes was found for CDH1 missense variants of unknown significance. CDH1 PV/LPVs occurred often in families with lobular breast cancer who did not fulfil the 2020 HDGC criteria, supporting the expansion of lobular breast cancer-centred criteria.\n\nEuropean Reference Network on Genetic Tumour Risk Syndromes, European Regional Development Fund, Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (Portugal), Cancer Research UK, and European Union's Horizon 2020 research and innovation programme.", "doi": "10.1016/S1470-2045(22)00643-X", "pmid": "36436516", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9810541"}, {"db": "pii", "key": "S1470-2045(22)00643-X"}], "notes": [], "created": "2023-11-22T21:40:56.923Z", "modified": "2023-11-22T21:40:56.936Z"}, {"entity": "publication", "iuid": "b22189adeaf145e4a32c95b246088b7b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b22189adeaf145e4a32c95b246088b7b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b22189adeaf145e4a32c95b246088b7b"}}, "title": "Artificial intelligence for diagnosis and grading of prostate cancer in biopsies: a population-based, diagnostic study.", "authors": [{"family": "Str\u00f6m", "given": "Peter", "initials": "P"}, {"family": "Kartasalo", "given": "Kimmo", "initials": "K"}, {"family": "Olsson", "given": "Henrik", "initials": "H"}, {"family": "Solorzano", "given": "Leslie", "initials": "L"}, {"family": "Delahunt", "given": "Brett", "initials": "B"}, {"family": "Berney", "given": "Daniel M", "initials": "DM"}, {"family": "Bostwick", "given": "David G", "initials": "DG"}, {"family": "Evans", "given": "Andrew J", "initials": "AJ"}, {"family": "Grignon", "given": "David J", "initials": "DJ"}, {"family": "Humphrey", "given": "Peter A", "initials": "PA"}, {"family": "Iczkowski", "given": "Kenneth A", "initials": "KA"}, {"family": "Kench", "given": "James G", "initials": "JG"}, {"family": "Kristiansen", "given": "Glen", "initials": "G"}, {"family": "van der Kwast", "given": "Theodorus H", "initials": "TH"}, {"family": "Leite", "given": "Katia R M", "initials": "KRM"}, {"family": "McKenney", "given": "Jesse K", "initials": "JK"}, {"family": "Oxley", "given": "Jon", "initials": "J"}, {"family": "Pan", "given": "Chin-Chen", "initials": "C"}, {"family": "Samaratunga", "given": "Hemamali", "initials": "H"}, {"family": "Srigley", "given": "John R", "initials": "JR"}, {"family": "Takahashi", "given": "Hiroyuki", "initials": "H"}, {"family": "Tsuzuki", "given": "Toyonori", "initials": "T"}, {"family": "Varma", "given": "Murali", "initials": "M"}, {"family": "Zhou", "given": "Ming", "initials": "M"}, {"family": "Lindberg", "given": "Johan", "initials": "J"}, {"family": "Lindskog", "given": "Cecilia", "initials": "C"}, {"family": "Ruusuvuori", "given": "Pekka", "initials": "P"}, {"family": "W\u00e4hlby", "given": "Carolina", "initials": "C", "orcid": "0000-0002-4139-7003", "researcher": {"href": "https://publications.scilifelab.se/researcher/c50194fbc8524d95b7152663ccf17f29.json"}}, {"family": "Gr\u00f6nberg", "given": "Henrik", "initials": "H"}, {"family": "Rantalainen", "given": "Mattias", "initials": "M"}, {"family": "Egevad", "given": "Lars", "initials": "L"}, {"family": "Eklund", "given": "Martin", "initials": "M"}], "type": "journal article", "published": "2020-02-00", "journal": {"title": "Lancet Oncol", "issn": "1474-5488", "issn-l": null, "volume": "21", "issue": "2", "pages": "222-232"}, "abstract": "An increasing volume of prostate biopsies and a worldwide shortage of urological pathologists puts a strain on pathology departments. Additionally, the high intra-observer and inter-observer variability in grading can result in overtreatment and undertreatment of prostate cancer. To alleviate these problems, we aimed to develop an artificial intelligence (AI) system with clinically acceptable accuracy for prostate cancer detection, localisation, and Gleason grading.\r\n\r\nWe digitised 6682 slides from needle core biopsies from 976 randomly selected participants aged 50-69 in the Swedish prospective and population-based STHLM3 diagnostic study done between May 28, 2012, and Dec 30, 2014 (ISRCTN84445406), and another 271 from 93 men from outside the study. The resulting images were used to train deep neural networks for assessment of prostate biopsies. The networks were evaluated by predicting the presence, extent, and Gleason grade of malignant tissue for an independent test dataset comprising 1631 biopsies from 246 men from STHLM3 and an external validation dataset of 330 biopsies from 73 men. We also evaluated grading performance on 87 biopsies individually graded by 23 experienced urological pathologists from the International Society of Urological Pathology. We assessed discriminatory performance by receiver operating characteristics and tumour extent predictions by correlating predicted cancer length against measurements by the reporting pathologist. We quantified the concordance between grades assigned by the AI system and the expert urological pathologists using Cohen's kappa.\r\n\r\nThe AI achieved an area under the receiver operating characteristics curve of 0\u00b7997 (95% CI 0\u00b7994-0\u00b7999) for distinguishing between benign (n=910) and malignant (n=721) biopsy cores on the independent test dataset and 0\u00b7986 (0\u00b7972-0\u00b7996) on the external validation dataset (benign n=108, malignant n=222). The correlation between cancer length predicted by the AI and assigned by the reporting pathologist was 0\u00b796 (95% CI 0\u00b795-0\u00b797) for the independent test dataset and 0\u00b787 (0\u00b784-0\u00b790) for the external validation dataset. For assigning Gleason grades, the AI achieved a mean pairwise kappa of 0\u00b762, which was within the range of the corresponding values for the expert pathologists (0\u00b760-0\u00b773).\r\n\r\nAn AI system can be trained to detect and grade cancer in prostate needle biopsy samples at a ranking comparable to that of international experts in prostate pathology. Clinical application could reduce pathology workload by reducing the assessment of benign biopsies and by automating the task of measuring cancer length in positive biopsy cores. An AI system with expert-level grading performance might contribute a second opinion, aid in standardising grading, and provide pathology expertise in parts of the world where it does not exist.\r\n\r\nSwedish Research Council, Swedish Cancer Society, Swedish eScience Research Center, EIT Health.", "doi": "10.1016/S1470-2045(19)30738-7", "pmid": "31926806", "labels": {"BioImage Informatics": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "S1470-2045(19)30738-7"}], "notes": [], "created": "2020-11-30T10:32:29.345Z", "modified": "2024-01-16T13:48:42.995Z"}], "created": "2020-11-30T10:32:29.354Z", "modified": "2020-11-30T10:32:29.354Z"}