PMID- 37934954
OWN - NLM
STAT- Publisher
LR  - 20231107
IS  - 1543-2165 (Electronic)
IS  - 0003-9985 (Linking)
DP  - 2023 Nov 7
TI  - Clinicopathologic Features of Breast Carcinoma With 2018 American Society of 
      Clinical Oncology/College of American Pathologists Fluorescence In Situ 
      Hybridization Group 3 (Human Epidermal Growth Factor Receptor 2 Chromosome 17 
      Centromere Ratio <2.0 and Average Human Epidermal Growth Factor Receptor 2 Copy 
      Number >/=6.0) Breast Cancers.
LID - 10.5858/arpa.2023-0275-OA [doi]
AB  - CONTEXT.-: The American Society of Clinical Oncology/College of American 
      Pathologists 2018 update of the human epidermal growth factor receptor 2 (HER2) 
      testing guideline includes a fluorescence in situ hybridization (FISH) group with 
      a HER2 to chromosome 17 centromere (CEP17) ratio less than 2.0 and HER2 copy 
      number 6.0 or greater (group 3), which requires integrated review of HER2 
      immunohistochemistry (IHC). OBJECTIVE.-: To assess the clinicopathologic features 
      of group 3 patients and determine features associated with HER2-positive status 
      after workup. DESIGN.-: Cases submitted for HER2 FISH between January 2019 and 
      June 2022 were identified, and relevant clinicopathologic information was 
      obtained. RESULTS.-: One hundred forty-two HER2 FISH cases (1.6%) were group 3. 
      In 52 cases (36.6%) IHC was negative (0/1+), in 3 (2.8%) IHC was positive (3+), 
      and in 86 (60.6%) IHC was 2+. Annotated IHC 2+ slides were recounted by a second 
      reviewer in targeted areas, where 16 of 86 (18.6%) had a HER2:CEP17 ratio less 
      than 2.0 and a HER2 copy number of 4.0 or greater to less than 6.0 (HER2 
      negative). After combined IHC/FISH review, 74 of 142 (52.1%) were classified as 
      HER2 positive. HER2 copy number/cell was higher in HER2-positive compared with 
      HER2-negative cases after the workup. The extent and intensity of staining in IHC 
      2+ cases did not correlate with the level of gene amplification. Twenty percent 
      of HER2-positive patients achieved pathologic complete response. CONCLUSIONS.-: 
      About half of group 3 cases were classified as HER2 positive after additional 
      workup. Pathologic complete response rates in HER2-positive cases were lower than 
      expected for group 1 (HER2:CEP17 ratio >/=2.0; HER2 copy number >/=4.0) patients. IHC 
      targeted FISH recounts may be redundant and may potentially lead to 
      classification of some patients as HER2 negative, resulting in withholding of 
      targeted therapy.
CI  - (c) 2023 College of American Pathologists.
FAU - Wilcock, Diane
AU  - Wilcock D
AD  - From ARUP Laboratories, Salt Lake City, Utah (Wilcock).
FAU - Sirohi, Deepika
AU  - Sirohi D
AD  - the Department of Pathology and Laboratory Medicine, Huntsman Cancer Institute, 
      University of Utah Health, Salt Lake City (Sirohi, Albertson, Cleary, Coleman, 
      Jedrzkiewicz, Mahlow, Ruano, Gulbahce).
FAU - Albertson, Daniel
AU  - Albertson D
AD  - the Department of Pathology and Laboratory Medicine, Huntsman Cancer Institute, 
      University of Utah Health, Salt Lake City (Sirohi, Albertson, Cleary, Coleman, 
      Jedrzkiewicz, Mahlow, Ruano, Gulbahce).
FAU - Cleary, Allison S
AU  - Cleary AS
AD  - the Department of Pathology and Laboratory Medicine, Huntsman Cancer Institute, 
      University of Utah Health, Salt Lake City (Sirohi, Albertson, Cleary, Coleman, 
      Jedrzkiewicz, Mahlow, Ruano, Gulbahce).
FAU - Coleman, Joshua F
AU  - Coleman JF
AD  - the Department of Pathology and Laboratory Medicine, Huntsman Cancer Institute, 
      University of Utah Health, Salt Lake City (Sirohi, Albertson, Cleary, Coleman, 
      Jedrzkiewicz, Mahlow, Ruano, Gulbahce).
FAU - Jedrzkiewicz, Jolanta
AU  - Jedrzkiewicz J
AD  - the Department of Pathology and Laboratory Medicine, Huntsman Cancer Institute, 
      University of Utah Health, Salt Lake City (Sirohi, Albertson, Cleary, Coleman, 
      Jedrzkiewicz, Mahlow, Ruano, Gulbahce).
FAU - Mahlow, Jonathan
AU  - Mahlow J
AD  - the Department of Pathology and Laboratory Medicine, Huntsman Cancer Institute, 
      University of Utah Health, Salt Lake City (Sirohi, Albertson, Cleary, Coleman, 
      Jedrzkiewicz, Mahlow, Ruano, Gulbahce).
FAU - Ruano, Ana L
AU  - Ruano AL
AD  - the Department of Pathology and Laboratory Medicine, Huntsman Cancer Institute, 
      University of Utah Health, Salt Lake City (Sirohi, Albertson, Cleary, Coleman, 
      Jedrzkiewicz, Mahlow, Ruano, Gulbahce).
FAU - Gulbahce, H Evin
AU  - Gulbahce HE
AD  - the Department of Pathology and Laboratory Medicine, Huntsman Cancer Institute, 
      University of Utah Health, Salt Lake City (Sirohi, Albertson, Cleary, Coleman, 
      Jedrzkiewicz, Mahlow, Ruano, Gulbahce).
LA  - eng
PT  - Journal Article
DEP - 20231107
PL  - United States
TA  - Arch Pathol Lab Med
JT  - Archives of pathology & laboratory medicine
JID - 7607091
SB  - IM
COIS- The authors have no relevant financial interest in the products or companies 
      described in this article.
EDAT- 2023/11/07 18:42
MHDA- 2023/11/07 18:42
CRDT- 2023/11/07 16:13
PHST- 2023/08/25 00:00 [accepted]
PHST- 2023/11/07 18:42 [medline]
PHST- 2023/11/07 18:42 [pubmed]
PHST- 2023/11/07 16:13 [entrez]
AID - 496776 [pii]
AID - 10.5858/arpa.2023-0275-OA [doi]
PST - aheadofprint
SO  - Arch Pathol Lab Med. 2023 Nov 7. doi: 10.5858/arpa.2023-0275-OA.