TY - JOUR
T1 - HER2 in Uterine Serous Carcinoma
T2 - Testing platforms and implications for targeted therapy
AU - Klc, Tenley R.
AU - Wu, Sharon
AU - Wilhite, Annelise M.
AU - Jones, Nathaniel L.
AU - Powell, Matthew A.
AU - Olawaiye, Alex
AU - Girda, Eugenia
AU - Brown, Jubilee
AU - Puechl, Allison
AU - Ali-Fehmi, Rouba
AU - Winer, Ira S.
AU - Herzog, Thomas J.
AU - Korn, W. Michael
AU - Erickson, Britt K.
N1 - Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/11
Y1 - 2022/11
N2 - 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.
AB - 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.
KW - Biomarkers
KW - Human epidermal growth factor receptor 2 HER2
KW - Uterine serous carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85138061099&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85138061099&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2022.09.006
DO - 10.1016/j.ygyno.2022.09.006
M3 - Article
C2 - 36114027
AN - SCOPUS:85138061099
SN - 0090-8258
VL - 167
SP - 289
EP - 294
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 2
ER -