Marshall E Kadin1, John Morgan2, Haiying Xu3, Caroline Glicksman4, David Sieber, William P Adams5, Pat McGuire6, Mark W Clemens7, Archana Thakur8, Lawrence G Lum8. 1. pathology and laboratory medicine (research), Brown University Alpert Medical School, Providence, RI, USA. 2. director of the Research Core Facility, Roger Williams Medical Center, Providence, RI, USA. 3. Roger Williams Medical Center, Providence, RI, USA. 4. Hackensack Meridian School of Medicine, Seton Hall, NJ, USA. 5. Department of Plastic Surgery, University of Texas Southwestern Medical School, Dallas, TX, USA. 6. Parkcrest Plastic Surgery, St Louis, MO, USA. 7. Department of Plastic Surgery, MD Anderson Cancer Center, Houston, TX, USA. 8. University of Virginia Cancer Center, Charlottesville, VA, USA.
Abstract
BACKGROUND: Granzyme B (GrB) is a serine protease secreted, along with pore-forming perforin, by cytotoxic lymphocytes to mediate apoptosis in target cells. GrB has been detected in tumor cells associated with systemic and breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) but its potential use for detection of early BIA-ALCL has not been fully investigated. OBJECTIVES: Prompted by the increased incidence of BIA-ALCL, the aim of this study was to assess GrB as a new biomarker to detect early disease in malignant seromas and to better understand the nature of the neoplastic cell. METHODS: A Human XL Cytokine Discovery Magnetic Luminex 45-plex Fixed Panel Performance Assay was used to compare cytokine levels in cell culture supernatants of BIA-ALCL and other T-cell lymphomas, as well as malignant and benign seromas surrounding breast implants. Immunohistochemistry was employed to localize GrB to cells in seromas and capsular infiltrates. RESULTS: Differences in GrB concentrations between malignant and benign seromas were significant (P < 0.001). GrB was found in and around apoptotic tumor cells, suggesting that the protease may be involved in tumor cell death. CONCLUSIONS: GrB is a useful marker for early detection of malignant seromas and to identify tumor cells in seromas and capsular infiltrates. Because there is an overlap between the lowest concentrations of soluble GrB in malignant seromas and the highest concentrations of GrB in benign seromas, it is recommended that GrB be used only as part of a panel of biomarkers for the screening and early detection of BIA-ALCL.
BACKGROUND: Granzyme B (GrB) is a serine protease secreted, along with pore-forming perforin, by cytotoxic lymphocytes to mediate apoptosis in target cells. GrB has been detected in tumor cells associated with systemic and breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) but its potential use for detection of early BIA-ALCL has not been fully investigated. OBJECTIVES: Prompted by the increased incidence of BIA-ALCL, the aim of this study was to assess GrB as a new biomarker to detect early disease in malignant seromas and to better understand the nature of the neoplastic cell. METHODS: A Human XL Cytokine Discovery Magnetic Luminex 45-plex Fixed Panel Performance Assay was used to compare cytokine levels in cell culture supernatants of BIA-ALCL and other T-cell lymphomas, as well as malignant and benign seromas surrounding breast implants. Immunohistochemistry was employed to localize GrB to cells in seromas and capsular infiltrates. RESULTS: Differences in GrB concentrations between malignant and benign seromas were significant (P < 0.001). GrB was found in and around apoptotic tumor cells, suggesting that the protease may be involved in tumor cell death. CONCLUSIONS: GrB is a useful marker for early detection of malignant seromas and to identify tumor cells in seromas and capsular infiltrates. Because there is an overlap between the lowest concentrations of soluble GrB in malignant seromas and the highest concentrations of GrB in benign seromas, it is recommended that GrB be used only as part of a panel of biomarkers for the screening and early detection of BIA-ALCL.
Authors: Bellinda A Bladergroen; Chris J L M Meijer; Rosita L ten Berge; C Erik Hack; Jettie J F Muris; Danny F Dukers; Andreas Chott; Yoshiaki Kazama; Joost J Oudejans; Oskar van Berkum; J Alain Kummer Journal: Blood Date: 2002-01-01 Impact factor: 22.113
Authors: C Laurent; A Delas; P Gaulard; C Haioun; A Moreau; L Xerri; A Traverse-Glehen; T Rousset; I Quintin-Roue; T Petrella; J F Emile; N Amara; P Rochaix; M P Chenard-Neu; A M Tasei; E Menet; H Chomarat; V Costes; L Andrac-Meyer; J F Michiels; C Chassagne-Clement; L de Leval; P Brousset; G Delsol; L Lamant Journal: Ann Oncol Date: 2015-11-23 Impact factor: 32.976