PMID- 36939053
OWN - NLM
STAT- MEDLINE
DCOM- 20230419
LR  - 20230922
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Linking)
VI  - 47
IP  - 5
DP  - 2023 May 1
TI  - HER2 IHC Expression and Gene Amplification in p53-aberrant High-grade Endometrial 
      Endometrioid Carcinoma Suggests That This Population May Benefit From HER2 
      Testing and Targeted Therapy.
PG  - 580-588
LID - 10.1097/PAS.0000000000002030 [doi]
AB  - Among gynecologic cancers, uterine serous carcinoma (USC) has been shown to be 
      human epidermal growth factor receptor 2 (HER2) amplified and trastuzumab has 
      been included in the recent National Comprehensive Cancer Network (NCCN) 
      guidelines for treatment of advanced stage or recurrent USC with HER2 
      overexpression/amplification. There is limited literature suggesting that a 
      subset of high-grade endometrioid carcinomas with aberrant p53 expression may 
      also be HER2 amplified and these patients could benefit from the addition of 
      targeted therapy. We identified 59 p53-aberrant (mismatch repair proficient) FIGO 
      3 endometrioid carcinomas of the uterus. HER2 immunohistochemistry was performed 
      in all 59 tumors and HER2 fluorescence in situ hybridization (FISH) was performed 
      in 52 of the 59 cases. Four of the 59 cases were HER2 3+ by immunohistochemistry 
      (6.7%), using the American Society of Clinical Oncology/College of American 
      Pathologists (ASCO/CAP) 2007, 2013, and 2018 criteria. HER2 FISH was performed in 
      3 of the 4 cases and was amplified in all 3. Nine, 8, and 7 tumors showed 2+ HER2 
      staining when applying 2018, 2013, and 2007 criteria, respectively, FISH was 
      performed in 7 tumors and none were amplified. An additional 4 cases did not 
      perfectly meet the 2018 ASCO/CAP criteria but were assigned a score of 2+, none 
      were amplified by HER2 FISH. The remaining 42 cases showed 1+ or no staining for 
      HER2, FISH was successfully performed in 38 tumors and none showed amplification. 
      Approximately half of the tumors fulfilled criteria for HER2-low or HER2-very low 
      (10 HER2-low and 20 HER2-very low). Our data shows that a subset of p53-aberrant 
      high-grade endometrial endometrioid carcinoma express HER2 and these patients may 
      benefit from the addition of targeted therapy. The role of targeted therapy in 
      HER2-low gynecologic carcinoma is currently unexplored.
CI  - Copyright (c) 2023 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Joehlin-Price, Amy S
AU  - Joehlin-Price AS
AD  - Cleveland Clinic, Cleveland, OH.
FAU - Komforti, Miglena K
AU  - Komforti MK
AD  - Mayo Clinic, Jacksonville, FL.
FAU - Ladwig, Nicholas R
AU  - Ladwig NR
AD  - University of California, San Francisco, San Francisco, CA.
FAU - Devine, Patrick
AU  - Devine P
AD  - University of California, San Francisco, San Francisco, CA.
FAU - Hoyle, Carrie
AU  - Hoyle C
AD  - Cleveland Clinic, Cleveland, OH.
FAU - McCoy, Lauren
AU  - McCoy L
AD  - Cleveland Clinic, Cleveland, OH.
FAU - Sprague, Cathy
AU  - Sprague C
AD  - Cleveland Clinic, Cleveland, OH.
FAU - Astbury, Caroline
AU  - Astbury C
AD  - Cleveland Clinic, Cleveland, OH.
FAU - Hoda, Raza
AU  - Hoda R
AD  - Cleveland Clinic, Cleveland, OH.
FAU - Chen, Yunn-Yi
AU  - Chen YY
AD  - University of California, San Francisco, San Francisco, CA.
FAU - Garg, Karuna
AU  - Garg K
AD  - Cleveland Clinic, Cleveland, OH.
LA  - eng
PT  - Journal Article
DEP - 20230320
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - 0 (Biomarkers, Tumor)
SB  - IM
MH  - Humans
MH  - Female
MH  - Gene Amplification
MH  - *Carcinoma, Endometrioid/genetics/therapy
MH  - Tumor Suppressor Protein p53/genetics/metabolism
MH  - In Situ Hybridization, Fluorescence
MH  - Receptor, ErbB-2
MH  - *Uterine Neoplasms/pathology
MH  - *Cystadenocarcinoma, Serous/genetics
MH  - *Breast Neoplasms/genetics
MH  - Biomarkers, Tumor/genetics
COIS- Conflicts of Interest and Source of Funding: The authors have disclosed that they 
      have no significant relationships with, or financial interest in, any commercial 
      companies pertaining to this article.
EDAT- 2023/03/21 06:00
MHDA- 2023/04/19 06:41
CRDT- 2023/03/20 07:03
PHST- 2023/04/19 06:41 [medline]
PHST- 2023/03/21 06:00 [pubmed]
PHST- 2023/03/20 07:03 [entrez]
AID - 00000478-202305000-00006 [pii]
AID - 10.1097/PAS.0000000000002030 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2023 May 1;47(5):580-588. doi: 10.1097/PAS.0000000000002030. 
      Epub 2023 Mar 20.