Automated quantitative RNA in situ hybridization for resolution of equivocal and heterogeneous ERBB2 (HER2) status in invasive breast carcinoma

Zhen Wang, Bryce P. Portier, Aaron M. Gruver, Son Bui, Hongwei Wang, Nan Su, Hong Thuy Vo, Xiao Jun Ma, Yuling Luo, G. Thomas Budd, Raymond R. Tubbs

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Patient management based on HER2 status in breast carcinoma is an archetypical example of personalized medicine but remains hampered by equivocal testing and intratumoral heterogeneity. We developed a fully automated, quantitative, bright-field in situ hybridization technique (RNAscope), applied it to quantify single-cell HER2 mRNA levels in 132 invasive breast carcinomas, and compared the results with those by real-time quantitative PCR (qPCR) and Food and Drug Administration-approved methods, including fluorescence in situ hybridization (FISH), IHC, chromogenic in situ hybridization, and dual in situ hybridization. Both RNAscope and qPCR were 97.3% concordant with FISH in cases in which FISH results were unequivocal. RNAscope was superior to qPCR in cases with intratumoral heterogeneity or equivocal FISH results. This novel assay may enable ultimate HER2 status resolution as a reflex test for current testing algorithms. Quantitative in situ RNA measurement at the single-cell level may be broadly applicable in companion diagnostic applications.

Original languageEnglish (US)
Pages (from-to)210-219
Number of pages10
JournalJournal of Molecular Diagnostics
Volume15
Issue number2
DOIs
StatePublished - Mar 2013

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Medicine

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