Integrated Molecular Characterization of HER2-Low Breast Cancer Using Next Generation Sequencing (NGS).

Fiche publication

Date publication

novembre 2023

Journal

Biomedicines

Auteurs

Membres identifiés du Cancéropôle Est :
Pr HARLE Alexandre , Dr LEROUX Agnès , Pr MERLIN Jean-Louis , Dr GILSON Pauline

Tous les auteurs :
Merlin JL, Husson M, Sahki N, Gilson P, Massard V, Harlé A, Leroux A

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/38137385

Résumé

Based on immunohistochemistry (IHC) and in situ hybridization (ISH), HER2-low breast cancers (BC) subtype-defined as IHC1+ or IHC2+/ISH- tumors-emerged and represent more than half of all BC. We evaluated the performance of NGS for integrated molecular characterization of HER2-low BC, including identification of actionable molecular targets, copy number variation (CNV), and microsatellite instability (MSI) analysis. Thirty-one BC specimens (11 HER2+, 10 HER2-, and 10 HER2-low) were routinely analyzed using IHC and ISH, and were selected and analyzed using NGS for gene mutations including , , , , , , and , CNV, and MSI. CNV values for the gene were significantly ( < 0.001) different between HER2+, and either HER2-low or HER2- tumors with mean values of 7.8 (SD = 6.8), 1.9 (SD = 0.3), and 2.0 (SD = 0.3), respectively. Using 3.25 as the cutoff value, 96.8% overall concordance of HER2 status was achieved between IHC and NGS compared to IHC and ISH. Using NGS, gene mutations and amplifications were detected in 68% (21/31) and 19% (6/31) of the cases, respectively. One case of MSI was detected in a HER2-negative and ISH unamplified case. Beside IHC, NGS allows the identification of HER2-low subtype simultaneously, with the detection of multiple actionable gene mutations being helpful for molecular board treatment selection.