Anna Marie Mulligan1, Dushanthi Pinnaduwage, Anita L Bane, Shelley B Bull, Frances P O'Malley, Irene L Andrulis. 1. Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital and the Department of Laboratory Medicine, St. Michael's Hospital, Toronto, Ontario, Canada; Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. mulligana@smh.toronto.on.ca.
Abstract
BACKGROUND: BRCA1-associated breast cancer had been shown to be morphologically and genetically distinct from sporadic cancers. The aim of this study was to determine the association of CK8/18 with BRCA1-associated tumors and if, by using CK8/18 and basal biomarkers in conjunction with morphologic features and family history characteristics, the specificity of the BRCA1-associated tumor profile in a pathologically well-characterized cohort would be improved. METHODS: Fifty-eight patients with known BRCA1 germline mutations and 221 control (familial non-BRCA) patients were selected from the Ontario Familial Breast Cancer Registry. From this database, information on family history and morphologic features was abstracted. Tissue microarrays were constructed and immunohistochemistry to determine expression of several biomarkers was performed. After a logistic regression fit, a best-subsets variable-selection procedure using model performance and predictive ability measures was applied to find a best predictor to distinguish BRCA1-associated tumors from non-BRCA associated tumors. RESULTS: BRCA1-associated tumors differed significantly from control tumors in terms of morphology, family history, and biomarker profile. CK8/18 was highly significantly associated with BRCA1 tumors. Consistently, BRCA1 cancers showed low levels of CK8/18 compared to non-BRCA tumors, whether they were basal-like or not. A combination of 7 factors, including CK8/18 and family history, best predicted the BRCA1-associated cancers. CONCLUSIONS: CK8/18 expression was independently associated with BRCA1-associated breast cancers. Reduced CK8/18 expression in conjunction with the basal-like phenotype and family history may have improved the ability to identify which tumors were likely to be associated with a BRCA1 germline mutation and thereby help streamline genetic testing.
BACKGROUND:BRCA1-associated breast cancer had been shown to be morphologically and genetically distinct from sporadic cancers. The aim of this study was to determine the association of CK8/18 with BRCA1-associated tumors and if, by using CK8/18 and basal biomarkers in conjunction with morphologic features and family history characteristics, the specificity of the BRCA1-associated tumor profile in a pathologically well-characterized cohort would be improved. METHODS: Fifty-eight patients with known BRCA1 germline mutations and 221 control (familial non-BRCA) patients were selected from the Ontario Familial Breast Cancer Registry. From this database, information on family history and morphologic features was abstracted. Tissue microarrays were constructed and immunohistochemistry to determine expression of several biomarkers was performed. After a logistic regression fit, a best-subsets variable-selection procedure using model performance and predictive ability measures was applied to find a best predictor to distinguish BRCA1-associated tumors from non-BRCA associated tumors. RESULTS:BRCA1-associated tumors differed significantly from control tumors in terms of morphology, family history, and biomarker profile. CK8/18 was highly significantly associated with BRCA1 tumors. Consistently, BRCA1 cancers showed low levels of CK8/18 compared to non-BRCA tumors, whether they were basal-like or not. A combination of 7 factors, including CK8/18 and family history, best predicted the BRCA1-associated cancers. CONCLUSIONS:CK8/18 expression was independently associated with BRCA1-associated breast cancers. Reduced CK8/18 expression in conjunction with the basal-like phenotype and family history may have improved the ability to identify which tumors were likely to be associated with a BRCA1 germline mutation and thereby help streamline genetic testing.
Authors: Y Miki; J Swensen; D Shattuck-Eidens; P A Futreal; K Harshman; S Tavtigian; Q Liu; C Cochran; L M Bennett; W Ding Journal: Science Date: 1994-10-07 Impact factor: 47.728
Authors: Torsten O Nielsen; Forrest D Hsu; Kristin Jensen; Maggie Cheang; Gamze Karaca; Zhiyuan Hu; Tina Hernandez-Boussard; Chad Livasy; Dave Cowan; Lynn Dressler; Lars A Akslen; Joseph Ragaz; Allen M Gown; C Blake Gilks; Matt van de Rijn; Charles M Perou Journal: Clin Cancer Res Date: 2004-08-15 Impact factor: 12.531
Authors: Dalia M Abd El-Rehim; Sarah E Pinder; Claire E Paish; J Bell; R W Blamey; John F R Robertson; Robert I Nicholson; Ian O Ellis Journal: J Pathol Date: 2004-06 Impact factor: 7.996
Authors: R A Lothe; P Peltomäki; G I Meling; L A Aaltonen; M Nyström-Lahti; L Pylkkänen; K Heimdal; T I Andersen; P Møller; T O Rognum Journal: Cancer Res Date: 1993-12-15 Impact factor: 12.701
Authors: L A Aaltonen; P Peltomäki; J P Mecklin; H Järvinen; J R Jass; J S Green; H T Lynch; P Watson; G Tallqvist; M Juhola Journal: Cancer Res Date: 1994-04-01 Impact factor: 12.701
Authors: Amanda B Spurdle; Fergus J Couch; Michael T Parsons; Lesley McGuffog; Daniel Barrowdale; Manjeet K Bolla; Qin Wang; Sue Healey; Rita Schmutzler; Barbara Wappenschmidt; Kerstin Rhiem; Eric Hahnen; Christoph Engel; Alfons Meindl; Nina Ditsch; Norbert Arnold; Hansjoerg Plendl; Dieter Niederacher; Christian Sutter; Shan Wang-Gohrke; Doris Steinemann; Sabine Preisler-Adams; Karin Kast; Raymonda Varon-Mateeva; Steve Ellis; Debra Frost; Radka Platte; Jo Perkins; D Gareth Evans; Louise Izatt; Ros Eeles; Julian Adlard; Rosemarie Davidson; Trevor Cole; Giulietta Scuvera; Siranoush Manoukian; Bernardo Bonanni; Frederique Mariette; Stefano Fortuzzi; Alessandra Viel; Barbara Pasini; Laura Papi; Liliana Varesco; Rosemary Balleine; Katherine L Nathanson; Susan M Domchek; Kenneth Offitt; Anna Jakubowska; Noralane Lindor; Mads Thomassen; Uffe Birk Jensen; Johanna Rantala; Åke Borg; Irene L Andrulis; Alexander Miron; Thomas V O Hansen; Trinidad Caldes; Susan L Neuhausen; Amanda E Toland; Heli Nevanlinna; Marco Montagna; Judy Garber; Andrew K Godwin; Ana Osorio; Rachel E Factor; Mary B Terry; Timothy R Rebbeck; Beth Y Karlan; Melissa Southey; Muhammad Usman Rashid; Nadine Tung; Paul D P Pharoah; Fiona M Blows; Alison M Dunning; Elena Provenzano; Per Hall; Kamila Czene; Marjanka K Schmidt; Annegien Broeks; Sten Cornelissen; Senno Verhoef; Peter A Fasching; Matthias W Beckmann; Arif B Ekici; Dennis J Slamon; Stig E Bojesen; Børge G Nordestgaard; Sune F Nielsen; Henrik Flyger; Jenny Chang-Claude; Dieter Flesch-Janys; Anja Rudolph; Petra Seibold; Kristiina Aittomäki; Taru A Muranen; Päivi Heikkilä; Carl Blomqvist; Jonine Figueroa; Stephen J Chanock; Louise Brinton; Jolanta Lissowska; Janet E Olson; Vernon S Pankratz; Esther M John; Alice S Whittemore; Dee W West; Ute Hamann; Diana Torres; Hans Ulrich Ulmer; Thomas Rüdiger; Peter Devilee; Robert A E M Tollenaar; Caroline Seynaeve; Christi J Van Asperen; Diana M Eccles; William J Tapper; Lorraine Durcan; Louise Jones; Julian Peto; Isabel dos-Santos-Silva; Olivia Fletcher; Nichola Johnson; Miriam Dwek; Ruth Swann; Anita L Bane; Gord Glendon; Anna M Mulligan; Graham G Giles; Roger L Milne; Laura Baglietto; Catriona McLean; Jane Carpenter; Christine Clarke; Rodney Scott; Hiltrud Brauch; Thomas Brüning; Yon-Dschun Ko; Angela Cox; Simon S Cross; Malcolm W R Reed; Jan Lubinski; Katarzyna Jaworska-Bieniek; Katarzyna Durda; Jacek Gronwald; Thilo Dörk; Natalia Bogdanova; Tjoung-Won Park-Simon; Peter Hillemanns; Christopher A Haiman; Brian E Henderson; Fredrick Schumacher; Loic Le Marchand; Barbara Burwinkel; Frederik Marme; Harald Surovy; Rongxi Yang; Hoda Anton-Culver; Argyrios Ziogas; Maartje J Hooning; J Margriet Collée; John W M Martens; Madeleine M A Tilanus-Linthorst; Hermann Brenner; Aida Karina Dieffenbach; Volke Arndt; Christa Stegmaier; Robert Winqvist; Katri Pylkäs; Arja Jukkola-Vuorinen; Mervi Grip; Annika Lindblom; Sara Margolin; Vijai Joseph; Mark Robson; Rohini Rau-Murthy; Anna González-Neira; José Ignacio Arias; Pilar Zamora; Javier Benítez; Arto Mannermaa; Vesa Kataja; Veli-Matti Kosma; Jaana M Hartikainen; Paolo Peterlongo; Daniela Zaffaroni; Monica Barile; Fabio Capra; Paolo Radice; Soo H Teo; Douglas F Easton; Antonis C Antoniou; Georgia Chenevix-Trench; David E Goldgar Journal: Breast Cancer Res Date: 2014-12-23 Impact factor: 6.466
Authors: Anita Bane; Alicia Viloria-Petit; Dushanthi Pinnaduwage; Anna Marie Mulligan; Frances P O'Malley; Irene L Andrulis Journal: Breast Cancer Res Treat Date: 2013-06-28 Impact factor: 4.872
Authors: Elizabeth Santana Dos Santos; François Lallemand; Ambre Petitalot; Sandrine M Caputo; Etienne Rouleau Journal: Int J Mol Sci Date: 2020-05-28 Impact factor: 5.923