ERBB2 amplification status in 67 salivary duct carcinomas assessed by immunohistochemistry, fluorescence in situ hybridization, and targeted exome sequencing Journal Article
| Authors: | Ferguson, D. C.; Momeni Boroujeni, A.; Zheng, T.; Mohanty, A. S.; Ho, A. L.; Arcila, M. E.; Ross, D. S.; Dogan, S. |
| Article Title: | ERBB2 amplification status in 67 salivary duct carcinomas assessed by immunohistochemistry, fluorescence in situ hybridization, and targeted exome sequencing |
| Abstract: | Salivary duct carcinoma (SDC) is an aggressive salivary gland malignancy with poor survival. Approximately 30% SDC harbor HER2 amplification and response to trastuzumab has been reported. However, a systematic approach for HER2 status assessment in this tumor type has not been established. A total of 67 tumor samples were evaluated for HER2 protein overexpression or ERBB2 gene amplification using at least 2 methods: immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and/or targeted exome next-generation sequencing (NGS). NGS assessed ERBB2 copy number fold change (FC) and total copy number (TCN). HER2 status was first determined by IHC/FISH according to the 2018 ASCO/CAP breast cancer guidelines. FISH results, the “gold standard”, were compared with the NGS results. All (15/15) IHC positive, 35% (6/17) equivocal, and no (0/19) IHC negative SDC were HER2 amplified by FISH. HER2 FISH signal/cell showed a good correlation with FC (Spearman correlation: 0.708, R2: 0.501, p < 0.0001) and TCN (Spearman correlation: 0.763, R2: 0.582, p < 0.0001). Receiver operating characteristics curve estimation showed an area under curve (AUC) of 0.975 for ERBB2 FC. FC cutoff of ≥1.8 corresponded to an accuracy of 95.2% for ERBB2 amplification (Youden’s index: 0.84, sensitivity: 89.47%, specificity: 100%). FC < 1.3 could be reliably classified as ERBB2 not amplified and FC ≥ 1.3 and <1.8 as equivocal. TCN estimation showed AUC of 0.981. TCN cutoff of >6.0 corresponded to an accuracy of 92% for HER2 amplification (Youden’s index: 0.81, sensitivity: 81.2%, specificity: 100%). TCN < 4 could be reliably classified as ERBB2 not amplified and TCN ≥ 4.0 and ≤6.0 as equivocal. FC and TCN were binarized with respective cutoffs of ≥1.8 and ≥6.0 and the proportion of agreement with FISH were 95% and 92%, respectively. The assessment of ERBB2 copy number by NGS is accurate and reliable with FC or TCN nearly equivalent to FISH in identifying HER2 amplified SDC. © 2021, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology. |
| Keywords: | immunohistochemistry; controlled study; human tissue; protein expression; major clinical study; genetics; area under the curve; comparative study; cancer diagnosis; diagnostic accuracy; gold standard; sensitivity and specificity; metabolism; in situ hybridization, fluorescence; breast cancer; gene amplification; epidermal growth factor receptor 2; cohort analysis; practice guideline; pathology; breast neoplasms; tumor marker; fluorescence in situ hybridization; algorithm; breast tumor; receptor, erbb-2; salivary gland tumor; salivary gland neoplasms; heterozygosity loss; gene dosage; paget nipple disease; correlational study; receiver operating characteristic; carcinoma, ductal; copy number variation; erbb2 protein, human; antibody labeling; salivary duct carcinoma; salivary gland duct; procedures; exome; high throughput sequencing; youden index; allelic imbalance; humans; human; female; article; mcnemar test; whole exome sequencing; biomarkers, tumor; salivary ducts |
| Journal Title: | Modern Pathology |
| Volume: | 35 |
| Issue: | 7 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2022-07-01 |
| Start Page: | 895 |
| End Page: | 902 |
| Language: | English |
| DOI: | 10.1038/s41379-021-00999-0 |
| PUBMED: | 34963694 |
| PROVIDER: | scopus |
| PMCID: | PMC10363285 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 August 2022 -- Source: Scopus |
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