PMID- 28862261
OWN - NLM
STAT- MEDLINE
DCOM- 20190107
LR  - 20230210
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Print)
IS  - 0893-3952 (Linking)
VI  - 31
IP  - 1
DP  - 2018 Jan
TI  - Molecular testing for the clinical diagnosis of fibrolamellar carcinoma.
PG  - 141-149
LID - 10.1038/modpathol.2017.103 [doi]
AB  - Fibrolamellar carcinoma has a distinctive morphology and immunophenotype, 
      including cytokeratin 7 and CD68 co-expression. Despite the distinct findings, 
      accurate diagnosis of fibrolamellar carcinoma continues to be a challenge. 
      Recently, fibrolamellar carcinomas were found to harbor a characteristic somatic 
      gene fusion, DNAJB1-PRKACA. A break-apart fluorescence in situ hybridization 
      (FISH) assay was designed to detect this fusion event and to examine its 
      diagnostic performance in a large, multicenter, multinational study. Cases 
      initially classified as fibrolamellar carcinoma based on histological features 
      were reviewed from 124 patients. Upon central review, 104 of the 124 cases were 
      classified histologically as typical of fibrolamellar carcinoma, 12 cases as 
      'possible fibrolamellar carcinoma' and 8 cases as 'unlikely to be fibrolamellar 
      carcinoma'. PRKACA FISH was positive for rearrangement in 102 of 103 (99%) 
      typical fibrolamellar carcinomas, 9 of 12 'possible fibrolamellar carcinomas' and 
      0 of 8 cases 'unlikely to be fibrolamellar carcinomas'. Within the 
      morphologically typical group of fibrolamellar carcinomas, two tumors with 
      unusual FISH patterns were also identified. Both cases had the fusion gene 
      DNAJB1-PRKACA, but one also had amplification of the fusion gene and one had 
      heterozygous deletion of the normal PRKACA locus. In addition, 88 conventional 
      hepatocellular carcinomas were evaluated with PRKACA FISH and all were negative. 
      These findings demonstrate that FISH for the PRKACA rearrangement is a clinically 
      useful tool to confirm the diagnosis of fibrolamellar carcinoma, with high 
      sensitivity and specificity. A diagnosis of fibrolamellar carcinoma is more 
      accurate when based on morphology plus confirmatory testing than when based on 
      morphology alone.
FAU - Graham, Rondell P
AU  - Graham RP
AUID- ORCID: 0000-0002-8686-4867
AD  - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
FAU - Yeh, Matthew M
AU  - Yeh MM
AUID- ORCID: 0000-0002-7430-2939
AD  - Department of Pathology, University of Washington, Seattle, WA, USA.
FAU - Lam-Himlin, Dora
AU  - Lam-Himlin D
AD  - Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ, 
      USA.
FAU - Roberts, Lewis R
AU  - Roberts LR
AD  - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
FAU - Terracciano, Luigi
AU  - Terracciano L
AD  - Division of Molecular Pathology, Institute of Pathology, University Hospital 
      Basel, Basel, Switzerland.
FAU - Cruise, Michael W
AU  - Cruise MW
AD  - Department of Pathology, Cleveland Clinic, Cleveland, OH, USA.
FAU - Greipp, Patricia T
AU  - Greipp PT
AD  - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
FAU - Zreik, Riyam T
AU  - Zreik RT
AUID- ORCID: 0000-0002-4102-3562
AD  - Department of Pathology, Baylor Scott & White Memorial Hospital, Temple, TX, USA.
FAU - Jain, Dhanpat
AU  - Jain D
AD  - Department of Pathology, Yale, New Haven, CT, USA.
FAU - Zaid, Nida
AU  - Zaid N
AD  - Department of Pathology, Microbiology and Immunology, Vanderbilt University, 
      Nashville, TN, USA.
FAU - Salaria, Safia N
AU  - Salaria SN
AD  - Department of Pathology, Microbiology and Immunology, Vanderbilt University, 
      Nashville, TN, USA.
FAU - Jin, Long
AU  - Jin L
AD  - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
FAU - Wang, Xiaoke
AU  - Wang X
AD  - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
FAU - Rustin, Jeanette G
AU  - Rustin JG
AD  - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
FAU - Kerr, Sarah E
AU  - Kerr SE
AD  - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
FAU - Sukov, William R
AU  - Sukov WR
AD  - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
FAU - Solomon, David A
AU  - Solomon DA
AD  - Department of Pathology, University of California San Francisco, San Francisco, 
      CA, USA.
FAU - Kakar, Sanjay
AU  - Kakar S
AD  - Department of Pathology, University of California San Francisco, San Francisco, 
      CA, USA.
FAU - Waterhouse, Emily
AU  - Waterhouse E
AD  - Department of Pathology, University of California San Francisco, San Francisco, 
      CA, USA.
FAU - Gill, Ryan M
AU  - Gill RM
AUID- ORCID: 0000-0001-6229-7928
AD  - Department of Pathology, University of California San Francisco, San Francisco, 
      CA, USA.
FAU - Ferrell, Linda
AU  - Ferrell L
AD  - Department of Pathology, University of California San Francisco, San Francisco, 
      CA, USA.
FAU - Alves, Venancio Af
AU  - Alves VA
AD  - Instituto do Cancer do Estado de Sao Paulo, Faculdade de Medicina da Universidade 
      de, Sao Paulo, Brazil.
FAU - Nart, Deniz
AU  - Nart D
AD  - Department of Pathology, Ege University, Izmir, Turkey.
FAU - Yilmaz, Funda
AU  - Yilmaz F
AD  - Department of Pathology, Ege University, Izmir, Turkey.
FAU - Roessler, Stephanie
AU  - Roessler S
AUID- ORCID: 0000-0002-5333-5942
AD  - Institute of Pathology, University Hospital, Heidelberg, Germany.
FAU - Longerich, Thomas
AU  - Longerich T
AD  - Institute of Pathology, University Hospital RWTH, Aachen, Germany.
FAU - Schirmacher, Peter
AU  - Schirmacher P
AD  - Institute of Pathology, University Hospital, Heidelberg, Germany.
FAU - Torbenson, Michael S
AU  - Torbenson MS
AD  - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
LA  - eng
GR  - P30 DK026743/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
DEP - 20170901
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 (DNAJB1 protein, human)
RN  - 0 (HSP40 Heat-Shock Proteins)
RN  - 0 (Oncogene Proteins, Fusion)
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  - Adult
MH  - Biomarkers, Tumor/*genetics
MH  - Carcinoma, Hepatocellular/*diagnosis/*genetics
MH  - Cyclic AMP-Dependent Protein Kinase Catalytic Subunits/genetics
MH  - Female
MH  - HSP40 Heat-Shock Proteins/genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Male
MH  - Oncogene Proteins, Fusion/genetics
MH  - Retrospective Studies
MH  - Young Adult
PMC - PMC5758901
COIS- The authors declare no conflict of interest.
EDAT- 2017/09/02 06:00
MHDA- 2019/01/08 06:00
PMCR- 2018/01/09
CRDT- 2017/09/02 06:00
PHST- 2017/02/15 00:00 [received]
PHST- 2017/06/23 00:00 [revised]
PHST- 2017/06/29 00:00 [accepted]
PHST- 2017/09/02 06:00 [pubmed]
PHST- 2019/01/08 06:00 [medline]
PHST- 2017/09/02 06:00 [entrez]
PHST- 2018/01/09 00:00 [pmc-release]
AID - S0893-3952(22)01729-X [pii]
AID - 10.1038/modpathol.2017.103 [doi]
PST - ppublish
SO  - Mod Pathol. 2018 Jan;31(1):141-149. doi: 10.1038/modpathol.2017.103. Epub 2017 
      Sep 1.