Multifactorial Analysis of Differences Between Sporadic Breast Cancers and Cancers Involving BRCA1 and BRCA2 Mutations (original) (raw)

Journal Article

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Department of Histopathology

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University College of London Medical School, U.K

Correspondence to : M. R. Stratton, M.D., Ph.D., Haddow Laboratories, Institute of Cancer Research, 15 Cotswold Rd., Sutton, Surrey SM2 5NG, U.K. E-mail: mikes@icr.ac.uk

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Departement d'Oncologie-Genetique et Laboratoire d'Anatomie et de Cytologie Pathologiques, Institut National de la Santé et de la Recherche Médicale CRI 9703

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Institut Paoli-Calmettes, Marseille, France

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Department of Pathology

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University of Liverpool, U.K.

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Sections of Cancer Genetics, Epidemiology, and Cell Biology and Experimental Pathology, Institute of Cancer Research, Haddow Laboratories

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Sutton, Surrey, U.K

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Department of Pathology

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The University of Edinburgh Medical School, U.K.

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The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Amsterdam

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Department of Pathology and Laboratory Medicine

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University of Pennsylvania Medical Center, Philadelphia;

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Peter MacCallum Cancer Institute, Melbourne, Australia, and Department of Pathology, University of Melbourne, Parkville, Victoria, Australia

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Statistical Laboratory, Department of Pure Mathematics and Mathematical Statistics, Cambridge, U.K

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Cancer Research Campaign Genetic Epidemiology Group, Department of Community Medicine

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Institute of Public Health, University of Cambridge, U.K.

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Revision received:

18 May 1997

Received:

28 October 1997

Published:

05 August 1998

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Sunil R. Lakhani, Jocelyne Jacquemier, John P. Sloane, Barry A. Gusterson, Thomas J. Anderson, Marc J. van de Vijver, Linda M. Farid, Deon Venter, Antonios Antoniou, Amy Storfer-Isser, Elizabeth Smyth, C. Michael Steel, Neva Haites, Rodney J. Scott,, David Goldgar, Susan Neuhausen, Peter A. Daly, Wilma Ormiston, Ross McManus, Siegfried Scherneck, Bruce A. J. Ponder, Debbie Ford, Julian Peto, Dominique Stoppa-Lyonnet, Yves-Jean Bignon, Jeffery P. Struewing, Nigel K. Spurr, D. Timothy Bishop, J. G. M. Klijn, Peter Devilee, Cees J. Cornelisse, Christine Lasset, Gilbert Lenoir, Rosa Bjork Barkardottir, Valgardur Egilsson, Ute Hamann, Jenny Chang-Claude, Hagay Sobol, Barbara Weber, Michael R. Stratton, Douglas F. Easton, Multifactorial Analysis of Differences Between Sporadic Breast Cancers and Cancers Involving BRCA1 and BRCA2 Mutations, JNCI: Journal of the National Cancer Institute, Volume 90, Issue 15, 5 August 1998, Pages 1138–1145, https://doi.org/10.1093/jnci/90.15.1138
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Abstract

Background : We have previously demonstrated that breast cancers associated with inherited BRCA1 and BRCA2 gene mutations differ from each other in their histopathologic appearances and that each of these types differs from breast cancers in patients unselected for family history (i.e., sporadic cancers). We have now conducted a more detailed examination of cytologic and architectural features of these tumors. Methods : Specimens of tumor tissue (5-µm-thick sections) were examined independently by two pathologists, who were unaware of the case or control subject status, for the presence of cell mitosis, lymphocytic infiltration, continuous pushing margins, and solid sheets of cancer cells; cell nuclei, cell nucleoli, cell necrosis, and cell borders were also evaluated. The resulting data were combined with previously available information on tumor type and tumor grade and further evaluated by multifactorial analysis. All statistical tests are two-sided. Results: Cancers associated with BRCA1 mutations exhibited higher mitotic counts (P = .001), a greater proportion of the tumor with a continuous pushing margin (P<.0001), and more lymphocytic infiltration (P = .002) than sporadic (i.e., control) cancers. Cancers associated with BRCA2 mutations exhibited a higher score for tubule formation (fewer tubules) (P = .0002), a higher proportion of the tumor perimeter with a continuous pushing margin (P<.0001), and a lower mitotic count (P = .003) than control cancers. Conclusions : Our study has identified key features of the histologic phenotypes of breast cancers in carriers of mutant BRCA1 and BRCA2 genes. This information may improve the classification of breast cancers in individuals with a family history of the disease and may ultimately aid in the clinical management of patients. [J Natl Cancer Inst 1998;90:1138–45]

© 1998 Oxford University Press

Topic:

• mutation
• cancer
• brca1 protein
• brca1 gene
• brca2 gene
• neoplasms
• breast cancer

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