PMID- 37406350
OWN - NLM
STAT- MEDLINE
DCOM- 20231216
LR  - 20231216
IS  - 1538-7151 (Electronic)
IS  - 0277-1691 (Linking)
VI  - 43
IP  - 1
DP  - 2024 Jan 1
TI  - HER2 Status Assessment in Endometrial Serous Carcinoma: Comparative Analysis of 
      Two Proposed Testing and Interpretation Algorithms.
PG  - 4-14
LID - 10.1097/PGP.0000000000000943 [doi]
AB  - HER2 status is now routinely assessed in endometrial serous carcinoma (ESC) due 
      to the reported predictive value of HER2 protein overexpression and/or gene 
      amplification. Herein the authors compare 2 proposed testing and interpretation 
      guidelines for HER2 in ESC. Forty-three consecutive cases of ESC that had been 
      dually tested by both HER2 immunohistochemistry (IHC) and fluorescence in situ 
      hybridization (FISH) were interpreted using 2 sets of guidelines. Guideline set 1 
      (GS1) is the 2018 American Society of Clinical Oncology/College of American 
      Pathologists guidelines for breast cancer. Guideline set 2 (GS2) is a recent 
      proposal that is a slight modification of the enrollment criteria for the 
      clinical trial (NCT01367002) that demonstrated a survival benefit for anti-HER2 
      therapy in ESC. By IHC, GS1 and GS2, respectively classified 39.5% (17/43) and 
      28% (12/43) of ESC as HER2-negative, 37.2% (16/43) and 53.4% (23/43) as HER2 
      equivocal, and 23.2% (10/43) and 18.6% (8/43) as HER2-positive ( P > 0.05 for 
      all). IHC and FISH were highly concordant at the extremes using either set of 
      guidelines, as no cases were found to be IHC3+/FISH-negative or IHC 
      0-1+/FISH-positive. GS1 and GS2 were comparable regarding the proportion of IHC 
      equivocal cases that were HER2 amplified by FISH (19% vs 23% respectively; [ P = 
      0.71]). GS1 and GS2 displayed 98% (42/43) concordance regarding the final (IHC 
      and/or FISH-based) classification of tumors as being HER2-positive or negative, 
      and the same 13 cases were ultimately classified as HER2 amplified using either 
      GS1 or GS2. One "discordant" case was classified as HER2-positive using GS2 but 
      HER2-negative using GS1 (HER2 IHC score 2+ using both guidelines, HER2:CEP17 
      signal ratio of 3, HER2 signal number of 3.4). Six (14%) of the 43 cases (FISH 
      Groups: 2, 3, and 4) would require IHC results to interpret the FISH findings 
      using GS1. Because GS1 requires that the HER2 IHC staining be observed within a 
      homogeneous and contiguous invasive cell population, and this is not a 
      requirement in GS2, GS2 may be better suited for ESC given its frequently 
      heterogeneous staining pattern. Additional studies may be required on the optimal 
      interpretation of problematic dual-probe FISH scenarios in GS2 and the necessity 
      for IHC correlation in such scenarios. Using either set of guidelines, our 
      findings support a reflex testing strategy of restricting FISH testing to cases 
      that are IHC equivocal.
CI  - Copyright (c) 2023 by the International Society of Gynecological Pathologists.
FAU - Hashem, Sherin
AU  - Hashem S
FAU - Zare, Somaye Y
AU  - Zare SY
FAU - Fadare, Oluwole
AU  - Fadare O
LA  - eng
PT  - Journal Article
DEP - 20230609
PL  - United States
TA  - Int J Gynecol Pathol
JT  - International journal of gynecological pathology : official journal of the 
      International Society of Gynecological Pathologists
JID - 8214845
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - 0 (Biomarkers, Tumor)
SB  - IM
MH  - Female
MH  - Humans
MH  - Receptor, ErbB-2/metabolism
MH  - In Situ Hybridization, Fluorescence/methods
MH  - *Breast Neoplasms/pathology
MH  - Gene Amplification
MH  - *Endometrial Neoplasms/diagnosis/genetics
MH  - *Carcinoma/genetics
MH  - Biomarkers, Tumor/metabolism
COIS- The authors declare no conflict of interest.
EDAT- 2023/07/05 19:12
MHDA- 2023/12/17 09:43
CRDT- 2023/07/05 17:02
PHST- 2023/12/17 09:43 [medline]
PHST- 2023/07/05 19:12 [pubmed]
PHST- 2023/07/05 17:02 [entrez]
AID - 00004347-990000000-00087 [pii]
AID - 10.1097/PGP.0000000000000943 [doi]
PST - ppublish
SO  - Int J Gynecol Pathol. 2024 Jan 1;43(1):4-14. doi: 10.1097/PGP.0000000000000943. 
      Epub 2023 Jun 9.