HER2 in Uterine Serous Carcinoma: Testing platforms and implications for targeted therapy.

Autor: Klc TR; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology University of Minnesota, Minneapolis, MN, USA., Wu S; Caris Life Sciences, Phoenix, AZ, United States of America., Wilhite AM; Mitchell Cancer Institute, University of South Alabama, Mobile, AL, United States of America., Jones NL; Mitchell Cancer Institute, University of South Alabama, Mobile, AL, United States of America., Powell MA; Washington University in St. Louis, St. Louis, MO, United States of America., Olawaiye A; University of Pittsburgh, Pittsburgh, PA, United States of America., Girda E; Rutgers Cancer Institute of New Jersey, Rutgers Health, New Brunswick, NJ, United States of America., Brown J; Levine Cancer Institute, Atrium Health, Charlotte, NC, United States of America., Puechl A; Levine Cancer Institute, Atrium Health, Charlotte, NC, United States of America., Ali-Fehmi R; Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States of America., Winer IS; Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States of America., Herzog TJ; University of Cincinnati Cancer Institute, Cincinnati, OH, United States of America., Korn WM; Caris Life Sciences, Phoenix, AZ, United States of America., Erickson BK; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology University of Minnesota, Minneapolis, MN, USA. Electronic address: bkeric@umn.edu.
Jazyk: angličtina
Zdroj: Gynecologic oncology [Gynecol Oncol] 2022 Nov; Vol. 167 (2), pp. 289-294. Date of Electronic Publication: 2022 Sep 14.
DOI: 10.1016/j.ygyno.2022.09.006
Abstrakt: Objective: HER2 is an important prognostic and therapeutic target in uterine serous carcinoma (USC). Optimal HER2 testing platforms have not been defined and guidelines for testing have changed over time. Our objective is to assess the concordance of HER2 positivity based on chromogenic in situ hybridization (CISH), immunohistochemistry (IHC), and next generation sequencing (NGS) and to determine the rate of downstream mutations that may affect response to HER2 directed therapy.
Methods: Utilizing the Caris tumor registry, 2192 USC tumors were identified and analyzed using NGS (NextSeq, 592 Genes and WES, NovaSEQ), IHC, and CISH. PD-L1 expression was tested by IHC. Microsatellite instability was tested by fragment analysis, IHC, and NGS. Tumor mutational burden (TMB) was measured by totaling somatic mutations per tumor. HER2 positivity through IHC and CISH was determined based on 2007 and 2018 ASCO/CAP HER2 breast cancer guidelines.
Results: There was a higher rate of HER2 positivity by IHC when using the 2018 guidelines compared to the 2007 guidelines (16.3% vs 12.3%). Concordance between IHC and CISH was 98.9%. ERBB2 amplification was identified by NGS in 10.5% of tumors. Compared to CISH results, this corresponds to a concordance rate of 91.6% and a positive predictive value (PPV) of 60.3%. Single gene alterations in HER2 amplified tumors that may implicate HER2 therapy resistance included PI3K (33.1%), KRAS (2.5%), and PTEN (1.3%).
Conclusions: There was high concordance between HER2 positivity based on CISH and IHC. Rate of HER2 positivity is the lowest by NGS. Ultimately these testing platforms need to be validated by response to targeted therapy.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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