PMID- 35777788
OWN - NLM
STAT- MEDLINE
DCOM- 20220706
LR  - 20220720
IS  - 1550-8080 (Electronic)
IS  - 0091-7370 (Linking)
VI  - 52
IP  - 3
DP  - 2022 May
TI  - The Use of Fluorescence in situ Hybridization to Confirm PRKACA Gene 
      Rearrangement in Fibrolamellar Hepatocellular Carcinoma: A Validation Study.
PG  - 475-483
AB  - OBJECTIVE: The objectives of this study are to define the specificity of the 
      DNAJB1-PRKACA fusion transcript for the fibrolamellar subtype of hepatocellular 
      carcinoma (FL-HCC) by testing a targeted sampling of other hepatic 
      neoplasms/proliferations and extrahepatic neoplasms seen in children and young 
      adults and to develop a FISH assay using a commercially available PRKACA break 
      apart probe for use in a CLIA-certified clinical laboratory. METHODS: Formalin 
      fixed paraffin embedded tissue sections from 12 FL-HCC cases, 142 cases of other 
      hepatic neoplasms/proliferations (conventional HCC, focal nodular hyperplasia 
      (FNH), hepatocellular adenoma (HA) and hepatoblastoma (HB)) and extrahepatic 
      neoplasms (neuroblastoma (NB), Wilms tumor (WT) and Gastrointestinal 
      neuroendocrine tumor (GNET)) and 60 matched background normal control tissues 
      underwent fluorescence in situ hybridization (FISH) testing using a break apart 
      probe targeting the PRKACA gene locus on chromosome 19 using standard techniques. 
      RESULTS: The PRKACA gene rearrangement was detected in 11/12 (92%) FL-HCC cases 
      and 1/94 (1%) of conventional HCC cases. All other cases and background control 
      tissues were negative for the PRKACA gene rearrangement. These findings establish 
      a test sensitivity of 91.7% and specificity of 99.5%. CONCLUSION: This study 
      shows that, using standard techniques, FISH testing with a commercially available 
      break apart probe targeting the PRKACA gene can be used as a surrogate for the 
      DNAJB1-PRKACA fusion commonly found in FL-HCC. Also, the PRKACA gene 
      rearrangement is not expressed in other hepatic neo-plasms/proliferations or 
      extrahepatic neoplasms seen in children and young adults. Finally, FISH testing 
      can be used as a diagnostic tool to confirm the diagnosis of FL-HCC, in the 
      appropriate clinical setting.
CI  - (c) 2022 by the Association of Clinical Scientists, Inc.
FAU - Weiel, Julianna J
AU  - Weiel JJ
AD  - Department of Pathology, Stanford University School of Medicine, Stanford.
FAU - Forgo, Balint
AU  - Forgo B
AD  - Department of Pathology, Stanford University School of Medicine, Stanford.
FAU - Sage, Julien
AU  - Sage J
AD  - Departments of Pediatrics and Genetics, Stanford University School of Medicine, 
      Stanford.
FAU - Rangaswami, Arun
AU  - Rangaswami A
AD  - Department of Pediatrics, University of California San Francisco, San Francisco, 
      CA, USA.
FAU - Hazard, Florette K
AU  - Hazard FK
AD  - Department of Pathology, Stanford University School of Medicine, Stanford 
      hazard@stanford.edu.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Ann Clin Lab Sci
JT  - Annals of clinical and laboratory science
JID - 0410247
RN  - 0 (DNAJB1 protein, human)
RN  - 0 (HSP40 Heat-Shock Proteins)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinase Catalytic Subunits)
RN  - EC 2.7.11.11 (PRKACA protein, human)
RN  - Fibrolamellar hepatocellular carcinoma
SB  - IM
MH  - *Carcinoma, Hepatocellular/genetics/pathology
MH  - Chromosome Aberrations
MH  - *Cyclic AMP-Dependent Protein Kinase Catalytic Subunits/genetics
MH  - Gene Rearrangement/genetics
MH  - HSP40 Heat-Shock Proteins/genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/methods
MH  - *Liver Neoplasms/genetics/pathology
OTO - NOTNLM
OT  - DNAJB1-PRKACA
OT  - FISH
OT  - carcinoma
OT  - fibrolamellar
OT  - hepatocellular
OT  - liver
EDAT- 2022/07/02 06:00
MHDA- 2022/07/07 06:00
CRDT- 2022/07/01 20:43
PHST- 2022/07/01 20:43 [entrez]
PHST- 2022/07/02 06:00 [pubmed]
PHST- 2022/07/07 06:00 [medline]
AID - 52/3/475 [pii]
PST - ppublish
SO  - Ann Clin Lab Sci. 2022 May;52(3):475-483.