TY - JOUR
T1 - HER2 in uterine serous carcinoma
T2 - Current state and clinical perspectives
AU - Navarro Sanchez, Janira M.
AU - Finkelman, Brian S.
AU - Turner, Bradley M.
AU - Katerji, Hani
AU - Wang, Xi
AU - Varghese, Sharlin
AU - Wang, Tiannan
AU - Peng, Yan
AU - Hicks, David G.
AU - Zhang, Huina
N1 - Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved.
PY - 2023/10/1
Y1 - 2023/10/1
N2 - Uterine cancer has the highest incidence and the second-highest mortality rate among gynecologic malignancies in the United States. Although uterine serous carcinoma (USC) represents less than 10% of endometrial carcinomas, it accounts for a disproportionate 50% of tumor relapses and 40% of endometrial cancer deaths. Over the past decade, clinical trials have focused on finding better treatments for this aggressive subtype of endometrial cancer, especially HER2-targeted therapy. Methods: We conducted a literature search in PubMed to expand the understanding of HER2 in USC. Results: HER2 has been established as an important biomarker with prognostic and therapeutic implications in USC. Intratumoral heterogeneity and lateral/basolateral membranous staining of HER2 as well as high discordance between HER2 immunohistochemistry and in situ hybridization are more common in USC than in breast carcinoma. Therefore, a universal HER2 testing and scoring system more suitable to endometrial cancer is needed and currently under investigation. Conclusions: This review discusses the clinical perspective of HER2 overexpression/gene amplification in USC, the distinct HER2 staining pattern and the evaluation of HER2 in USC, the resistance mechanisms of HER2-targeted therapy in HER2-positive cancers, and likely areas of future investigation.
AB - Uterine cancer has the highest incidence and the second-highest mortality rate among gynecologic malignancies in the United States. Although uterine serous carcinoma (USC) represents less than 10% of endometrial carcinomas, it accounts for a disproportionate 50% of tumor relapses and 40% of endometrial cancer deaths. Over the past decade, clinical trials have focused on finding better treatments for this aggressive subtype of endometrial cancer, especially HER2-targeted therapy. Methods: We conducted a literature search in PubMed to expand the understanding of HER2 in USC. Results: HER2 has been established as an important biomarker with prognostic and therapeutic implications in USC. Intratumoral heterogeneity and lateral/basolateral membranous staining of HER2 as well as high discordance between HER2 immunohistochemistry and in situ hybridization are more common in USC than in breast carcinoma. Therefore, a universal HER2 testing and scoring system more suitable to endometrial cancer is needed and currently under investigation. Conclusions: This review discusses the clinical perspective of HER2 overexpression/gene amplification in USC, the distinct HER2 staining pattern and the evaluation of HER2 in USC, the resistance mechanisms of HER2-targeted therapy in HER2-positive cancers, and likely areas of future investigation.
KW - ERBB2
KW - HER2
KW - intratumoral heterogeneity
KW - uterine serous carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85174080066&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85174080066&partnerID=8YFLogxK
U2 - 10.1093/ajcp/aqad056
DO - 10.1093/ajcp/aqad056
M3 - Review article
C2 - 37267036
AN - SCOPUS:85174080066
SN - 0002-9173
VL - 160
SP - 341
EP - 351
JO - American journal of clinical pathology
JF - American journal of clinical pathology
IS - 4
ER -