TEST:

PathVysion HER-2 DNA Probe Kit

HER2 status was determined by IHC/FISH and NGS in 45 cases: 19 serous, 18 high-grade (unspecified histologic type, HGU), 5 endometrioid 1 carcinosarcoma, 1 undifferentiated and 1 gastric- type. IHC-FISH HER2 was positive in 11/45 (24.4%) of cases, all serous or HGU. NGS identified 3 cases as amplified (concordant) and 1 non-pathogenic SNV.

Conclusion In our institution, about half of the requests for HER2 testing occurred in non-serous EC cases reflecting the notion that histologic subtyping of high grade EC is challenging as well as the limited management options for advanced EC. The frequent observation of intratumoral heterogeneity raises the need to further study its potential role in trastuzumab resistance, benchmarking and possible rational of testing antibody drug conjugates in endometrial carcinoma.

CMA can help us understand and resolve challenging ERBB2 results. Further studies are warranted to examine the utility of CMA in facilitating ERBB2 testing, especially in cases with unusual results.

We detected variable HER2 expression in both primary and metastatic NSCLCs. HER2 overexpression and copy-number amplification were found more frequently in ADC, particularly in tumors metastasized to CNS. Membranous, but not cytoplasmic/nuclear IHC staining pattern was correlated with copy-number amplification.

Background Conventional pathologic scoring of HER2 by IHC is proven to distinguish potential responders to trastuzumab but has not been effective for next generation antibody drug conjugates (ADCs) such as trastuzumab deruxtecan (T-DXd), which is capable of bystander killing...Further clinical verification and validation on large cohorts is needed. Footnote: This study was approved by the IRB at MSKCC.

RC48-ADC, a novel humanized anti-HER2 antibody conjugated with monomethyl auristatin E, has shown a promising efficacy in patients with HER2-positive locally advanced or metastatic urothelial carcinoma (mUC)... The modified HER2 testing scoring system could be applied to UC to determine which patient might benefit from anti-HER2-ADC treatment. There was a trend towards a better benefit for patients with HER2 amplification and the tumor heterogeneity did not influence the drug efficacy.

" HER2 mRNA overexpression was not a feature in our group of patients. Based on our data, breast cancers with HER2 IHC2+ and in FISH group 2 support a categorization of HER2 negative."

"We observed 27.2% reclassification rate by using 2013 guidelines compared to 2007, lower threshold for positive (from equivocal, 20.7% of patients re-classified to positive and 6.5% to negative HER2 status). In contrast, the 2018 updates eliminated the FISH equivocal category with concomitant Her2IHC correlation and additional scoring of tumor nuclei. Implementing 2018 CAP guidelines led to 100% reclassification of 2007 equivocal cases into in 81.7% negative cases and 18.3% positive for HER2 status."