PMID- 34663915
OWN - NLM
STAT- MEDLINE
DCOM- 20220428
LR  - 20230210
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Linking)
VI  - 35
IP  - 4
DP  - 2022 Apr
TI  - RAI1 alternate probe identifies additional gastroesophageal adenocarcinoma cases 
      as amplified following equivocal HER2 fluorescence in situ hybridization testing: 
      experience from a national reference laboratory.
PG  - 549-553
LID - 10.1038/s41379-021-00933-4 [doi]
AB  - The College of American Pathologists/American Society of Clinical Oncology 
      recommends HER2 testing prior to initiation of targeted therapy for patients with 
      advanced Gastroesophageal adenocarcinoma (GEA), using immunohistochemistry (IHC) 
      followed by fluorescence in situ hybridization (FISH) in cases with an equivocal 
      (score 2 + ) result on IHC. The FISH results are considered indeterminate if the 
      HER2/CEP17 ratio is <2.0 with an average CEP17 copy number of >/=3.0 and a HER2 
      copy number >/=4.0 and </=6.0 after counting additional tumor cells. Indeterminate 
      results may be resolved by using an alternative chromosome 17 probe such as RAI1. 
      The purpose of this study is to review our experience with RAI1 alternate probe 
      in HER2 FISH testing of GEA in a large reference laboratory setting. Esophageal, 
      gastroesophageal, and gastric adenocarcinomas received for HER2 FISH testing in 
      our lab between 9/2018 and 1/2020 were included. HER2/CEP17 and HER2/ RAI1 
      ratios, and the average HER2, CEP17, RAI1 signals per cell were recorded. 328 GEA 
      had HER2 testing performed in our lab during the study period. 101 (30.8%) were 
      amplified, 169 (51.5%) were non-amplified and 58 (17.7%) were indeterminate. 
      Following RAI1 testing, 42 (72.4%) of 58 indeterminate cases were reclassified as 
      non-amplified and 16 (27.6%) were reclassified as amplified, increasing the total 
      amplified cases to 117 (35.7%). The correlation between the average CEP17 and 
      RAI1 copy number for all cases was weak (R(2) = 0.095). In summary, using the 
      alternate probe RAI1 reclassifies 27.6% of original HER2 FISH indeterminate 
      gastroesophageal carcinomas as amplified, which makes them eligible for targeted 
      therapies.
CI  - (c) 2021. The Author(s), under exclusive licence to United States & Canadian 
      Academy of Pathology.
FAU - Jedrzkiewicz, Jolanta
AU  - Jedrzkiewicz J
AD  - Department of Pathology, University of Utah, Salt Lake City, UT, USA.
FAU - Sirohi, Deepika
AU  - Sirohi D
AD  - Department of Pathology, University of Utah, Salt Lake City, UT, USA.
FAU - Uvejzovic, Nermin
AU  - Uvejzovic N
AD  - ARUP Labs, Salt Lake City, UT, USA.
FAU - Gulbahce, H Evin
AU  - Gulbahce HE
AD  - Department of Pathology, University of Utah, Salt Lake City, UT, USA. 
      evin.gulbahce@path.utah.edu.
LA  - eng
PT  - Journal Article
DEP - 20211018
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - *Adenocarcinoma/genetics
MH  - Biomarkers, Tumor/genetics
MH  - *Breast Neoplasms
MH  - Chromosomes, Human, Pair 17/genetics
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Receptor, ErbB-2/genetics
EDAT- 2021/10/20 06:00
MHDA- 2022/04/29 06:00
CRDT- 2021/10/19 06:23
PHST- 2021/07/15 00:00 [received]
PHST- 2021/09/17 00:00 [accepted]
PHST- 2021/09/17 00:00 [revised]
PHST- 2021/10/20 06:00 [pubmed]
PHST- 2022/04/29 06:00 [medline]
PHST- 2021/10/19 06:23 [entrez]
AID - S0893-3952(22)00300-3 [pii]
AID - 10.1038/s41379-021-00933-4 [doi]
PST - ppublish
SO  - Mod Pathol. 2022 Apr;35(4):549-553. doi: 10.1038/s41379-021-00933-4. Epub 2021 
      Oct 18.