PAM50 breast cancer subtyping by RT-qPCR and concordance with standard clinical molecular markers
Bastien, Roy R. L. (The ARUP Institute for Clinical and Experimental Pathology (Salt Lake City, Estats Units d'Amèrica))
Rodríguez-Lescure, Álvaro (Hospital General Universitario de Elche)
Ebbert, Mark T. W. (The ARUP Institute for Clinical and Experimental Pathology (Salt Lake City, Estats Units d'Amèrica))
Prat, Aleix (Universitat Autònoma de Barcelona. Departament de Medicina)
Munárriz, Blanca (Hospital Universitari i Politècnic La Fe (València))
Rowe, Leslie (The ARUP Institute for Clinical and Experimental Pathology (Salt Lake City, Estats Units d'Amèrica))
Miller, Patricia (The ARUP Institute for Clinical and Experimental Pathology (Salt Lake City, Estats Units d'Amèrica))
Ruiz Borrego, Manuel (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Anderson, Daniel (The ARUP Institute for Clinical and Experimental Pathology (Salt Lake City, Estats Units d'Amèrica))
Lyons, Bradley (The ARUP Institute for Clinical and Experimental Pathology (Salt Lake City, Estats Units d'Amèrica))
Álvarez López, Isabel (Hospital Universitario de Donostia (Sant Sebastià, País Basc))
Dowell, Tracy (The ARUP Institute for Clinical and Experimental Pathology (Salt Lake City, Estats Units d'Amèrica))
Wall, David (The ARUP Institute for Clinical and Experimental Pathology (Salt Lake City, Estats Units d'Amèrica))
Seguí, Miguel Ángel (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Barley, Lee (The ARUP Institute for Clinical and Experimental Pathology (Salt Lake City, Estats Units d'Amèrica))
Boucher, Kenneth M. (Huntsman Cancer Institute (Salt Lake City, Estats Units d'Amèrica))
Alba, Emilio (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Pappas, Lisa (Huntsman Cancer Institute (Salt Lake City, Estats Units d'Amèrica))
Davis, Carole A. (Huntsman Cancer Institute (Salt Lake City, Estats Units d'Amèrica))
Aranda, Ignacio (Hospital General Universitario de Alicante (Alacant, País Valencià))
Fauron, Christiane (The ARUP Institute for Clinical and Experimental Pathology (Salt Lake City, Estats Units d'Amèrica))
Stijleman, Inge J. (Huntsman Cancer Institute (Salt Lake City, Estats Units d'Amèrica))
Palacios, José (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Antón, Antonio (Hospital Universitario Miguel Servet (Saragossa))
Carrasco, Eva (GEICAM. Spanish Breast Cancer Research Group (Madrid))
Caballero, Rosalía (GEICAM. Spanish Breast Cancer Research Group (Madrid))
Ellis, Matthew J. (Washington University. Department of Oncology (St. Louis, Estats Units d'Amèrica))
Nielsen, Torsten O. (University of British Columbia. Department of Anatomical Pathology (Vancouver, Canadà))
Perou, Charles M. (University of North Carolina at Chapel Hill. Lineberger Comprehensive Cancer Center (Chapel Hill, Estats Units d'Amèrica))
Astill, Mark (The ARUP Institute for Clinical and Experimental Pathology (Salt Lake City, Estats Units d'Amèrica))
Bernard, Philip S. (Huntsman Cancer Institute (Salt Lake City, Estats Units d'Amèrica))
Martín Jiménez, Miguel (Hospital General Universitario Gregorio Marañón)

Date:	2012
Abstract:	Background: Many methodologies have been used in research to identify the "intrinsic" subtypes of breast cancer commonly known as Luminal A, Luminal B, HER2-Enriched (HER2-E) and Basal-like. The PAM50 gene set is often used for gene expression-based subtyping; however, surrogate subtyping using panels of immunohistochemical (IHC) markers are still widely used clinically. Discrepancies between these methods may lead to different treatment decisions. Methods: We used the PAM50 RT-qPCR assay to expression profile 814 tumors from the GEICAM/9906 phase III clinical trial that enrolled women with locally advanced primary invasive breast cancer. All samples were scored at a single site by IHC for estrogen receptor (ER), progesterone receptor (PR), and Her2/neu (HER2) protein expression. Equivocal HER2 cases were confirmed by chromogenic in situ hybridization (CISH). Single gene scores by IHC/CISH were compared with RT-qPCR continuous gene expression values and "intrinsic" subtype assignment by the PAM50. High, medium, and low expression for ESR1, PGR, ERBB2, and proliferation were selected using quartile cut-points from the continuous RT-qPCR data across the PAM50 subtype assignments. Results: ESR1, PGR, and ERBB2 gene expression had high agreement with established binary IHC cut-points (area under the curve (AUC) ≥ 0. 9). Estrogen receptor positivity by IHC was strongly associated with Luminal (A and B) subtypes (92%), but only 75% of ER negative tumors were classified into the HER2-E and Basal-like subtypes. Luminal A tumors more frequently expressed PR than Luminal B (94% vs 74%) and Luminal A tumors were less likely to have high proliferation (11% vs 77%). Seventy-seven percent (30/39) of ER-/HER2+ tumors by IHC were classified as the HER2-E subtype. Triple negative tumors were mainly comprised of Basal-like (57%) and HER2-E (30%) subtypes. Single gene scoring for ESR1, PGR, and ERBB2 was more prognostic than the corresponding IHC markers as shown in a multivariate analysis. Conclusions: The standard immunohistochemical panel for breast cancer (ER, PR, and HER2) does not adequately identify the PAM50 gene expression subtypes. Although there is high agreement between biomarker scoring by protein immunohistochemistry and gene expression, the gene expression determinations for ESR1 and ERBB2 status was more prognostic.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	BMC medical genomics, Vol. 15, N. 44 (October 2012) , p. 1-9, ISSN 1755-8794

DOI: 10.1186/1755-8794-5-44
PMID: 23035882

12 p, 915.6 KB

Additional file 3 6 p, 65.6 KB

Additional file 6 3 p, 1.5 MB

Additional file 7 1 p, 1.6 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Parc Taulí Research and Innovation Institute (I3PT
Articles > Research articles
Articles > Published articles