PMID- 35701667
OWN - NLM
STAT- MEDLINE
DCOM- 20221027
LR  - 20231213
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Linking)
VI  - 35
IP  - 11
DP  - 2022 Nov
TI  - Nuclear expression of AFF2 C-terminus is a sensitive and specific ancillary 
      marker for DEK::AFF2 carcinoma of the sinonasal tract.
PG  - 1587-1595
LID - 10.1038/s41379-022-01117-4 [doi]
AB  - DEK::AFF2 carcinoma of the sinonasal tract is an emerging entity. The tumor is 
      typically characterized by papillary proliferation of non-keratinizing squamous 
      epithelial cells with monotonous cytologic features, which may mimic other 
      sinonasal tumors. The confirmation of this gene fusion has thus far relied solely 
      on next-generation sequencing, fluorescence in situ hybridization (FISH), or 
      reverse transcription polymerase chain reaction (RT-PCR). This current study 
      aimed to validate an immunohistochemical assay for AFF2 C-terminus as an 
      ancillary marker. We first analyzed publicly available RNA sequencing data of 
      sinonasal tumors from the national center for biotechnology information (NCBI) 
      sequence read archive and identified 3 DEK::AFF2 carcinomas out of 28 sinonasal 
      tumors. The gene expression of AFF2 was significantly higher in the 
      fusion-positive cases compared to the wild-type tumors (p < 0.001), while DEK was 
      not. We then optimized an immunohistochemical assay with an anti-AFF2 C-terminus 
      antibody for ancillary diagnosis. Seventeen DEK::AFF2 carcinomas, including 11 
      cases with predominantly low-grade morphology and one showing glandular 
      differentiation, as well as 78 DEK FISH-negative sinonasal tumors were evaluated 
      by AFF2 immunohistochemistry (IHC). Sixteen of the 17 DEK::AFF2 carcinomas showed 
      nuclear AFF2 expression in >/=30% of tumor cells, including one decalcified case 
      that failed FISH and RT-PCR confirmation. The one case that was negative for AFF2 
      IHC in the tumor cells also lacked expression in the internal positive control. 
      It was thus considered a failure of the IHC rather than a truly negative case and 
      was excluded from the statistical analysis. All DEK FISH-negative sinonasal 
      tumors were negative for nuclear AFF2 expression. The nuclear expression of AFF2 
      IHC showed 100% sensitivity and specificity for DEK::AFF2 carcinoma. Accordingly, 
      AFF2 IHC is a highly sensitive and specific ancillary marker that distinguishes 
      DEK-AFF2 carcinoma from the other sinonasal tumors with overlapping morphological 
      features and may be an especially useful alternative for decalcified specimens.
CI  - (c) 2022. The Author(s), under exclusive licence to United States & Canadian 
      Academy of Pathology.
FAU - Kuo, Ying-Ju
AU  - Kuo YJ
AD  - Department of Pathology and Laboratory Medicine, Taipei Veterans General 
      Hospital, Taipei, Taiwan.
AD  - School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
FAU - Lewis, James S Jr
AU  - Lewis JS Jr
AD  - Department of Pathology, Microbiology, and Immunology, Vanderbilt University 
      Medical Center, Nashville, TN, USA.
AD  - Department of Otolaryngology - Head and Neck Surgery, Vanderbilt University 
      Medical Center, Nashville, TN, USA.
FAU - Truong, Tra
AU  - Truong T
AD  - Department of Pathobiology and Laboratory Medicine, University of Toronto, 
      Toronto, ON, Canada.
AD  - Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, ON, 
      Canada.
FAU - Yeh, Yi-Chen
AU  - Yeh YC
AD  - Department of Pathology and Laboratory Medicine, Taipei Veterans General 
      Hospital, Taipei, Taiwan.
AD  - School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
AD  - Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, 
      Taipei, Taiwan.
FAU - Chernock, Rebecca D
AU  - Chernock RD
AUID- ORCID: 0000-0001-6253-0478
AD  - Department of Pathology and Immunology, Washington University in St. Louis, St. 
      Louis, MO, USA.
FAU - Zhai, Changwen
AU  - Zhai C
AD  - Department of Pathology, Eye, Ear, Nose and Throat Hospital, Fudan University, 
      Shanghai, China.
FAU - Chen, Yun-An
AU  - Chen YA
AD  - Department of Pathology and Laboratory Medicine, Taichung Veterans General 
      Hospital, Taichung, Taiwan.
FAU - Hongo, Takahiro
AU  - Hongo T
AD  - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Lee, Chien-Kuan
AU  - Lee CK
AD  - Department of Pathology, Kuang Tien General Hospital, Taichung, Taiwan.
FAU - Shi, Qiuying
AU  - Shi Q
AD  - Department of Pathology, Emory University, Atlanta, GA, USA.
FAU - Velez Torres, Jaylou M
AU  - Velez Torres JM
AD  - Department of Pathology and Laboratory Medicine, University of Miami Miller 
      School of Medicine, Miami, FL, USA.
FAU - Geromes, Ariana B
AU  - Geromes AB
AD  - Anatomic and Clinical Laboratory Associates, P.C, Nashville, TN, USA.
FAU - Chu, Ying-Hsia
AU  - Chu YH
AUID- ORCID: 0000-0002-8289-7418
AD  - Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, 
      Taoyuan, Taiwan.
FAU - Hsieh, Min-Shu
AU  - Hsieh MS
AUID- ORCID: 0000-0002-0594-3732
AD  - Department of Pathology, National Taiwan University Hospital and National Taiwan 
      University College of Medicine, Taipei, Taiwan.
AD  - Graduate Institute of Pathology, National Taiwan University College of Medicine, 
      Taipei, Taiwan.
FAU - Yamamoto, Hidetaka
AU  - Yamamoto H
AUID- ORCID: 0000-0001-9148-6445
AD  - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Weinreb, Ilan
AU  - Weinreb I
AD  - Department of Pathobiology and Laboratory Medicine, University of Toronto, 
      Toronto, ON, Canada.
AD  - Laboratory Medicine Program, University Health Network, Toronto, ON, Canada.
FAU - Hang, Jen-Fan
AU  - Hang JF
AUID- ORCID: 0000-0003-4299-2784
AD  - Department of Pathology and Laboratory Medicine, Taipei Veterans General 
      Hospital, Taipei, Taiwan. jfhang@vghtpe.gov.tw.
AD  - School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. 
      jfhang@vghtpe.gov.tw.
AD  - Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, 
      Taiwan. jfhang@vghtpe.gov.tw.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220614
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  - 0 (DEK protein, human)
RN  - 0 (Poly-ADP-Ribose Binding Proteins)
RN  - 0 (Chromosomal Proteins, Non-Histone)
RN  - 0 (Oncogene Proteins)
RN  - 0 (AFF2 protein, human)
RN  - 0 (Nuclear Proteins)
SB  - IM
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Biomarkers, Tumor/genetics/analysis
MH  - *Carcinoma/diagnosis/genetics/pathology
MH  - Immunohistochemistry
MH  - *Paranasal Sinuses/chemistry/pathology
MH  - Poly-ADP-Ribose Binding Proteins/genetics
MH  - Chromosomal Proteins, Non-Histone/genetics
MH  - Oncogene Proteins/genetics
MH  - Nuclear Proteins/genetics
EDAT- 2022/06/15 06:00
MHDA- 2022/10/28 06:00
CRDT- 2022/06/14 23:31
PHST- 2022/03/11 00:00 [received]
PHST- 2022/05/23 00:00 [accepted]
PHST- 2022/05/18 00:00 [revised]
PHST- 2022/06/15 06:00 [pubmed]
PHST- 2022/10/28 06:00 [medline]
PHST- 2022/06/14 23:31 [entrez]
AID - S0893-3952(22)00225-3 [pii]
AID - 10.1038/s41379-022-01117-4 [doi]
PST - ppublish
SO  - Mod Pathol. 2022 Nov;35(11):1587-1595. doi: 10.1038/s41379-022-01117-4. Epub 2022 
      Jun 14.