title: Biomarkers Provide Clues to Early Events in the Pathogenesis of Breast Implant-Associated Anaplastic Large Cell Lymphoma.
abstract: Almost 200 women worldwide have been diagnosed with breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). The unique location and specific lymphoma type strongly suggest an etio-pathologic link between breast implants and BIA-ALCL. It is postulated that chronic inflammation via bacterial infection may be an etiological factor. BIA-ALCL resembles primary cutaneous ALCL (pcALCL) in morphology, activated T-cell phenotype, and indolent clinical course. Gene expression array analysis, flow cytometry, and immunohistochemistry were used to study pcALCL and BIA-ALCL cell lines. Clinical samples were also studied to characterize transcription factor and cytokine profiles of tumor cells and surrounding lymphocytes. BIA-ALCL and pcALCL were found to have common expression of transcription factors SOCS3, JunB, SATB1, and a cytokine profile suggestive of a Th1 phenotype. Similar patterns were observed in a CD30+ cutaneous lymphoproliferative disorder (LPD). The patterns of cytokine and transcription factor expression suggest that BIA-ALCL is likely to arise from chronic bacterial antigen stimulation of T-cells. Further analysis of cytokine and transcription factor profiles may allow early detection and treatment of BIA-ALCL leading to better prognosis and survival. LEVEL OF EVIDENCE 5: Risk.
authors.affiliation: Dr Kadin is a Professor of Dermatology, Boston University School of Medicine, Boston, MA; and a Staff Physician, Roger Williams Medical Center, Providence, RI. Dr Deva is an Associate Professor of Cosmetic, Plastic, and Reconstructive Surgery, Macquarie University, NSW, Australia. Ms Xu is a Research Assistant, Dr Morgan is Director of the Research Core Facility, and Dr Khare is Director of the Cancer Immunotherapy and Gene Therapy Facility, Roger Williams Medical Center, Providence, RI. Dr MacLeod is Director of Cytogenetics at the Leibniz Institute, DSMZ - German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany. Dr Van Natta is an Associate Clinical Professor, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. Dr Adams is an Associate Clinical Professor, Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, TX. Dr Brody is Professor Emeritus in the Division of Plastic Surgery, and Dr Epstein is a Professor of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA.
authors.forename: Marshall E
authors.initials: ME
authors.lastname: Kadin
authors.affiliation: Dr Kadin is a Professor of Dermatology, Boston University School of Medicine, Boston, MA; and a Staff Physician, Roger Williams Medical Center, Providence, RI. Dr Deva is an Associate Professor of Cosmetic, Plastic, and Reconstructive Surgery, Macquarie University, NSW, Australia. Ms Xu is a Research Assistant, Dr Morgan is Director of the Research Core Facility, and Dr Khare is Director of the Cancer Immunotherapy and Gene Therapy Facility, Roger Williams Medical Center, Providence, RI. Dr MacLeod is Director of Cytogenetics at the Leibniz Institute, DSMZ - German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany. Dr Van Natta is an Associate Clinical Professor, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. Dr Adams is an Associate Clinical Professor, Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, TX. Dr Brody is Professor Emeritus in the Division of Plastic Surgery, and Dr Epstein is a Professor of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA.
authors.forename: Anand
authors.initials: A
authors.lastname: Deva
authors.affiliation: Dr Kadin is a Professor of Dermatology, Boston University School of Medicine, Boston, MA; and a Staff Physician, Roger Williams Medical Center, Providence, RI. Dr Deva is an Associate Professor of Cosmetic, Plastic, and Reconstructive Surgery, Macquarie University, NSW, Australia. Ms Xu is a Research Assistant, Dr Morgan is Director of the Research Core Facility, and Dr Khare is Director of the Cancer Immunotherapy and Gene Therapy Facility, Roger Williams Medical Center, Providence, RI. Dr MacLeod is Director of Cytogenetics at the Leibniz Institute, DSMZ - German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany. Dr Van Natta is an Associate Clinical Professor, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. Dr Adams is an Associate Clinical Professor, Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, TX. Dr Brody is Professor Emeritus in the Division of Plastic Surgery, and Dr Epstein is a Professor of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA.
authors.forename: Haiying
authors.initials: H
authors.lastname: Xu
authors.affiliation: Dr Kadin is a Professor of Dermatology, Boston University School of Medicine, Boston, MA; and a Staff Physician, Roger Williams Medical Center, Providence, RI. Dr Deva is an Associate Professor of Cosmetic, Plastic, and Reconstructive Surgery, Macquarie University, NSW, Australia. Ms Xu is a Research Assistant, Dr Morgan is Director of the Research Core Facility, and Dr Khare is Director of the Cancer Immunotherapy and Gene Therapy Facility, Roger Williams Medical Center, Providence, RI. Dr MacLeod is Director of Cytogenetics at the Leibniz Institute, DSMZ - German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany. Dr Van Natta is an Associate Clinical Professor, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. Dr Adams is an Associate Clinical Professor, Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, TX. Dr Brody is Professor Emeritus in the Division of Plastic Surgery, and Dr Epstein is a Professor of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA.
authors.forename: John
authors.initials: J
authors.lastname: Morgan
authors.affiliation: Dr Kadin is a Professor of Dermatology, Boston University School of Medicine, Boston, MA; and a Staff Physician, Roger Williams Medical Center, Providence, RI. Dr Deva is an Associate Professor of Cosmetic, Plastic, and Reconstructive Surgery, Macquarie University, NSW, Australia. Ms Xu is a Research Assistant, Dr Morgan is Director of the Research Core Facility, and Dr Khare is Director of the Cancer Immunotherapy and Gene Therapy Facility, Roger Williams Medical Center, Providence, RI. Dr MacLeod is Director of Cytogenetics at the Leibniz Institute, DSMZ - German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany. Dr Van Natta is an Associate Clinical Professor, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. Dr Adams is an Associate Clinical Professor, Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, TX. Dr Brody is Professor Emeritus in the Division of Plastic Surgery, and Dr Epstein is a Professor of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA.
authors.forename: Pranay
authors.initials: P
authors.lastname: Khare
authors.affiliation: Dr Kadin is a Professor of Dermatology, Boston University School of Medicine, Boston, MA; and a Staff Physician, Roger Williams Medical Center, Providence, RI. Dr Deva is an Associate Professor of Cosmetic, Plastic, and Reconstructive Surgery, Macquarie University, NSW, Australia. Ms Xu is a Research Assistant, Dr Morgan is Director of the Research Core Facility, and Dr Khare is Director of the Cancer Immunotherapy and Gene Therapy Facility, Roger Williams Medical Center, Providence, RI. Dr MacLeod is Director of Cytogenetics at the Leibniz Institute, DSMZ - German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany. Dr Van Natta is an Associate Clinical Professor, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. Dr Adams is an Associate Clinical Professor, Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, TX. Dr Brody is Professor Emeritus in the Division of Plastic Surgery, and Dr Epstein is a Professor of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA.
authors.forename: Roderick A F
authors.initials: RA
authors.lastname: MacLeod
authors.affiliation: Dr Kadin is a Professor of Dermatology, Boston University School of Medicine, Boston, MA; and a Staff Physician, Roger Williams Medical Center, Providence, RI. Dr Deva is an Associate Professor of Cosmetic, Plastic, and Reconstructive Surgery, Macquarie University, NSW, Australia. Ms Xu is a Research Assistant, Dr Morgan is Director of the Research Core Facility, and Dr Khare is Director of the Cancer Immunotherapy and Gene Therapy Facility, Roger Williams Medical Center, Providence, RI. Dr MacLeod is Director of Cytogenetics at the Leibniz Institute, DSMZ - German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany. Dr Van Natta is an Associate Clinical Professor, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. Dr Adams is an Associate Clinical Professor, Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, TX. Dr Brody is Professor Emeritus in the Division of Plastic Surgery, and Dr Epstein is a Professor of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA.
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Van Natta
authors.affiliation: Dr Kadin is a Professor of Dermatology, Boston University School of Medicine, Boston, MA; and a Staff Physician, Roger Williams Medical Center, Providence, RI. Dr Deva is an Associate Professor of Cosmetic, Plastic, and Reconstructive Surgery, Macquarie University, NSW, Australia. Ms Xu is a Research Assistant, Dr Morgan is Director of the Research Core Facility, and Dr Khare is Director of the Cancer Immunotherapy and Gene Therapy Facility, Roger Williams Medical Center, Providence, RI. Dr MacLeod is Director of Cytogenetics at the Leibniz Institute, DSMZ - German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany. Dr Van Natta is an Associate Clinical Professor, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. Dr Adams is an Associate Clinical Professor, Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, TX. Dr Brody is Professor Emeritus in the Division of Plastic Surgery, and Dr Epstein is a Professor of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA.
authors.forename: William P
authors.initials: WP
authors.lastname: Adams
authors.affiliation: Dr Kadin is a Professor of Dermatology, Boston University School of Medicine, Boston, MA; and a Staff Physician, Roger Williams Medical Center, Providence, RI. Dr Deva is an Associate Professor of Cosmetic, Plastic, and Reconstructive Surgery, Macquarie University, NSW, Australia. Ms Xu is a Research Assistant, Dr Morgan is Director of the Research Core Facility, and Dr Khare is Director of the Cancer Immunotherapy and Gene Therapy Facility, Roger Williams Medical Center, Providence, RI. Dr MacLeod is Director of Cytogenetics at the Leibniz Institute, DSMZ - German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany. Dr Van Natta is an Associate Clinical Professor, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. Dr Adams is an Associate Clinical Professor, Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, TX. Dr Brody is Professor Emeritus in the Division of Plastic Surgery, and Dr Epstein is a Professor of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA.
authors.forename: Garry S
authors.initials: GS
authors.lastname: Brody
authors.affiliation: Dr Kadin is a Professor of Dermatology, Boston University School of Medicine, Boston, MA; and a Staff Physician, Roger Williams Medical Center, Providence, RI. Dr Deva is an Associate Professor of Cosmetic, Plastic, and Reconstructive Surgery, Macquarie University, NSW, Australia. Ms Xu is a Research Assistant, Dr Morgan is Director of the Research Core Facility, and Dr Khare is Director of the Cancer Immunotherapy and Gene Therapy Facility, Roger Williams Medical Center, Providence, RI. Dr MacLeod is Director of Cytogenetics at the Leibniz Institute, DSMZ - German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany. Dr Van Natta is an Associate Clinical Professor, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. Dr Adams is an Associate Clinical Professor, Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, TX. Dr Brody is Professor Emeritus in the Division of Plastic Surgery, and Dr Epstein is a Professor of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Epstein
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D019928:Breast Implantation; D018427:Breast Implants / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017728:Lymphoma, Large-Cell, Anaplastic / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology*; D008875:Middle Aged; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D014157:Transcription Factors