Journal Article

Correlation between breast cancer subtypes determined by immunohistochemistry and n-COUNTER PAM50 assay: a real-world study

Jerez, Yolanda, Del Monte-Millán, María, Ocaña, Inmaculada, Herrero López, Blanca, Cebollero, María, Moreno Muñoz, Diana, Alvarez, Enrique, Martín, Miguel, Roche-Molina, Marta, Enrech, Santos, Moreno Anton, Fernando, Lopez-Tarruella, Sara, Arias, Ainhoa, Bueno Muiño, Coralia, Olier Garate, Clara, Echavarria Diaz-Guardamino, Isabel, García-Sáenz, José Ángel, Massarrah, Tatiana, Marrupe, David, Gamez Casado, Salvador, Lara Álvarez, Miguel Ángel, Marquez-Rodas, Iván

2024

Overview

Purpose Molecular subtyping based on gene expression profiling (i.e., PAM50 assay) aids in determining the prognosis and treatment of breast cancer (BC), particularly in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors, where luminal A and B subtypes have different prognoses and treatments. Several surrogate classifications have been proposed for distinguishing between the luminal A and B subtypes. This study determines the accuracy of local immunohistochemistry (IHC) techniques for classifying HR-positive/HER2-negative (HR+/HER2−) tumors according to intrinsic subtypes using the nCOUNTER PAM50 assay as reference and the HR status definition according the ASCO/CAP recommendations. Methods Molecular subtypes resulting from nCOUNTER PAM50 performed in our laboratory between 2014 and 2020 were correlated with three different proxy surrogates proposed in the literature based on ER, PR, HER2, and Ki67 expression with different cut-off values. Concordance was measured using the level of agreement and kappa statistics. Results From 1049 samples with the nCOUNTER test, 679 and 350 were luminal A and B subtypes, respectively. Only a poor-to-fair correlation was observed between the three proxy surrogates and real genomic subtypes as determined by nCOUNTER PAM50. Moreover, 5–11% and 18–36% of the nCOUNTER PAM50 luminal B and A tumors were classified as luminal A and B, respectively, by these surrogates. Conclusion The concordance between luminal subtypes determined by three different IHC-based classifiers and the nCOUNTER PAM50 assay was suboptimal. Thus, a significant proportion of luminal A and B tumors as determined by the surrogate classifiers could be undertreated or over-treated.

• Publisher: Springer US,Springer,Springer Nature B.V
• Subject: Biomarkers, Tumor - genetics / Biomarkers, Tumor - metabolism / Breast cancer / Breast Neoplasms - diagnosis / Breast Neoplasms - genetics / Breast Neoplasms - metabolism / Cancer / Cancer research / Care and treatment / Epidermal growth factor / ErbB-2 protein / Female / Gene expression / Gene Expression Profiling / Genes / Humans / Immunohistochemistry / Medicine / Medicine & Public Health / Oncology / Original Laboratory Investigation / Prognosis / Receptor, ErbB-2 - genetics / Receptor, ErbB-2 - metabolism / Receptors, Progesterone - genetics / Receptors, Progesterone - metabolism / Tumors