PAM50 Breast Cancer Subtyping by RT-qPCR and Concordance with Standard Clinical Molecular Markers

被引：235

作者：

Bastien, Roy R. L. ^{[1
]}

Rodriguez-Lescure, Alvaro ^{[2
]}

Ebbert, Mark T. W. ^{[1
]}

Prat, Aleix ^{[3
,4
,5
,6
]}

Munarriz, Blanca ^{[7
]}

Rowe, Leslie ^{[1
]}

Miller, Patricia ^{[1
]}

Ruiz-Borrego, Manuel ^{[8
]}

Anderson, Daniel ^{[1
]}

Lyons, Bradley ^{[1
]}

Alvarez, Isabel ^{[9
]}

Dowell, Tracy ^{[1
]}

Wall, David ^{[1
]}

Angel Segui, Miguel ^{[10
]}

Barley, Lee ^{[1
]}

Boucher, Kenneth M. ^{[11
]}

Alba, Emilio ^{[12
]}

Pappas, Lisa ^{[11
]}

Davis, Carole A. ^{[13
]}

Aranda, Ignacio ^{[14
]}

Fauron, Christiane ^{[1
]}

Stijleman, Inge J. ^{[13
]}

Palacios, Jose ^{[15
]}

Anton, Antonio ^{[16
]}

Carrasco, Eva ^{[17
]}

Caballero, Rosalia ^{[17
]}

Ellis, Matthew J. ^{[18
]}

Nielsen, Torsten O. ^{[19
]}

Perou, Charles M. ^{[3
,4
,5
]}

Astill, Mark ^{[1
]}

Bernard, Philip S. ^{[1
,13
]}

Martin, Miguel ^{[20
]}

机构：

[1] ARUP Inst Clin & Expt Pathol, Salt Lake City, UT USA

[2] Hosp Univ Elche, Dept Med Oncol, Elche, Spain

[3] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[4] Univ N Carolina, Dept Genet, Chapel Hill, NC USA

[5] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA

[6] Univ Autonoma Barcelona, Dept Med, E-08193 Barcelona, Spain

[7] Hosp Univ La Fe, Dept Med Oncol, Valencia, Spain

[8] Hosp Univ Virgen del Rocio, Dept Med Oncol, Seville, Spain

[9] Hosp Donostia, Dept Med Oncol, San Sebastian, Spain

[10] Corp Sanitaria Parc Tauli, Dept Med Oncol, Sabadell, Spain

[11] Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT 84112 USA

[12] Hosp Univ Virgen de la Victoria, Dept Med Oncol, Malaga, Spain

[13] Univ Utah, Hlth Sci Ctr, Dept Pathol, Huntsman Canc Inst, Salt Lake City, UT 84132 USA

[14] Hosp Gen Univ Alicante, Dept Pathol, Alicante, Spain

[15] Hosp Virgen del Rocio, Dept Pathol, Seville, Spain

[16] Hosp Univ Miguel Servet, Dept Med Oncol, Zaragoza, Spain

[17] GEICAM, Spanish Breast Canc Res Grp, Madrid, Spain

[18] Washington Univ, Dept Oncol, St Louis, MO USA

[19] Univ British Columbia, Dept Anat Pathol, Vancouver, BC V5Z 1M9, Canada

[20] Univ Complutense, Dept Med Oncol, Hosp Gen Univ Gregorio Maranon, E-28040 Madrid, Spain

来源：

BMC MEDICAL GENOMICS | 2012年 / 5卷

关键词：

GENE-EXPRESSION; INTRINSIC SUBTYPE; CLASSIFICATION; PCR; MICROARRAY; PORTRAITS; PREDICTOR; SURVIVAL; THERAPY; TUMORS;

D O I：

10.1186/1755-8794-5-44

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页数：12

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