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Abstract 2481: Concordance of PAM50 molecular subtyping between oligonucleotide microarray and nanoString nCounter assay for Taiwanese breast cancer

2020; American Association for Cancer Research; Volume: 80; Issue: 16_Supplement Linguagem: Inglês

10.1158/1538-7445.am2020-2481

1538-7445

Chi-Cheng Huang, Chao‐Chiang Tu, Mong‐Hsun Tsai, Liang‐Chuan Lai, Ching-Shui Huang,

Molecular Biology Techniques and Applications

Abstract Concordance of PAM50 molecular subtyping between oligonucleotide microarray and nanoString nCounter assay for Taiwanese breast cancer Introduction Breast cancer is molecularly heterogeneous and at least five molecular subtypes have been defined according to intrinsic genes transcription. Currently microarrays, RT-PCR, and next generation RNA sequencing have been adopted for subtyping in addition to the original nanoString nCounter assay. This study aimed to evaluate the consistency in subtyping Taiwanese breast cancers. Methods A total of 109 Taiwanese breast cancers (24 with adjacent normal breast) were assayed with Affymetrix Human Genome U133 plus 2.0 arrays and 96 were assayed with the customized 145-gene nanoString Codeset BCeCSig, of which the academic PAM50 was investigated. Of note, 64 patients were assayed for both platforms. Subtyping with the nearest centroid (single sample prediction) was called for each patient; Spearman's rank correlation coefficients were used, and samples were unclassified if correlation coefficients to all 5 centroids were less than 0.1. Results Table 1 showed the distributions of molecular subtypes with clinical IHC results. For 24 matched normal breast tissues, 21 were classified as normal breast-like. For 64 breast cancers (one unclassified) tested for both platforms, 41 (65%) were classified with identical subtype, resulting in a fair Kappa statistic of 0.55. Taking nCounter as gold standard, classification accuracy was 50% (3/6), 72% (13/18), 53% (10/19), 87% (13/15), and 40% (2/5) for basal-like, HER2-enriched, luminal-A, luminal-B, and normal breast-like subtype using Affymetrix microarray. ER-/HER2- phenotype and basal-like subtype experienced worse relapse free survival at 8-year follow-up (55.6% and 63.6% censored). Table 1.Molecular subtypes and IHC phenotypes (two unclassified and one missing IHC result).Subtype IHCBasal-likeHER2-enrichedLuminal-ALuminal-BNormal breast-likeHR+/HER2+276174HR+/HER2-6442429HR-/HER2+625209HR-/HER2-144003 Conclusions: Using public domain microarrays as a handy shortcut for breast cancer molecular subtyping is luring in scientific communities. Our experiments showed that fundamental discrepancy existed between distinct approaches, and more cation should be taken without too much extrapolation. On the other hand, adjacent normal breast tissue did display normal breast-like character, and this subtype should be viewed as a continuum of surrounding stroma. Citation Format: Chi-Cheng Huang, Chao-Chiang Tu, Mong-Hsun Tsai, Liang-chuan Lai, Ching-Shui Huang. Concordance of PAM50 molecular subtyping between oligonucleotide microarray and nanoString nCounter assay for Taiwanese breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2481.