PMID- 26596524
OWN - NLM
STAT- MEDLINE
DCOM- 20160930
LR  - 20240507
IS  - 1943-7811 (Electronic)
IS  - 1525-1578 (Linking)
VI  - 18
IP  - 1
DP  - 2016 Jan
TI  - Next-Generation Sequencing and Fluorescence in Situ Hybridization Have Comparable 
      Performance Characteristics in the Analysis of Pancreaticobiliary Brushings for 
      Malignancy.
PG  - 124-30
LID - S1525-1578(15)00222-6 [pii]
LID - 10.1016/j.jmoldx.2015.08.002 [doi]
AB  - Cytological evaluation of pancreatic or biliary duct brushings is a specific, but 
      insensitive, test for malignancy. We compared adjunctive molecular testing with 
      next-generation sequencing (NGS) relative to fluorescence in situ hybridization 
      (FISH) for detection of high-risk neoplasia or malignancy. Bile duct brushings 
      from 81 specimens were subjected to cytological analysis, FISH using the 
      UroVysion probe set, and targeted NGS. Specimens were placed into 
      negative/atypical (negative) or suspicious/positive (positive) categories 
      depending on cytology and negative or positive categories on the basis of FISH 
      and NGS results. Performance characteristics for each diagnostic modality were 
      calculated on the basis of clinicopathologic follow-up and compared in a receiver 
      operating characteristic analysis. There were 33 high-risk neoplasia/malignant 
      strictures (41%) and 48 benign (59%). NGS revealed driver mutations in 24 cases 
      (30%), including KRAS (21 of 24 cases), TP53 (14 of 24 cases), SMAD4 (6 of 24 
      cases), and CDKN2A (4 of 24 cases). Cytology had a sensitivity of 67% (95% CI, 
      48%-82%) and a specificity of 98% (95% CI, 89%-100%). When added to cytology, NGS 
      increased the sensitivity to 85% (95% CI, 68%-95%), leading to a significant 
      increase in the area under the curve in a receiver operating characteristic 
      analysis (P = 0.03). FISH increased the sensitivity to 76% (95% CI, 58%-89%), 
      without significantly increasing the area under the curve. These results suggest 
      that ancillary NGS testing offers advantages over FISH, although studies with 
      larger cohorts are needed to verify these findings.
CI  - Copyright (c) 2016 American Society for Investigative Pathology and the Association 
      for Molecular Pathology. Published by Elsevier Inc. All rights reserved.
FAU - Dudley, Jonathan C
AU  - Dudley JC
AD  - Department of Pathology, Harvard Medical School, Massachusetts General Hospital, 
      Boston, Massachusetts.
FAU - Zheng, Zongli
AU  - Zheng Z
AD  - Department of Pathology, Harvard Medical School, Massachusetts General Hospital, 
      Boston, Massachusetts.
FAU - McDonald, Thomas
AU  - McDonald T
AD  - Department of Pathology, Harvard Medical School, Massachusetts General Hospital, 
      Boston, Massachusetts.
FAU - Le, Long P
AU  - Le LP
AD  - Department of Pathology, Harvard Medical School, Massachusetts General Hospital, 
      Boston, Massachusetts.
FAU - Dias-Santagata, Dora
AU  - Dias-Santagata D
AD  - Department of Pathology, Harvard Medical School, Massachusetts General Hospital, 
      Boston, Massachusetts.
FAU - Borger, Darrell
AU  - Borger D
AD  - Department of Pathology, Harvard Medical School, Massachusetts General Hospital, 
      Boston, Massachusetts.
FAU - Batten, Julie
AU  - Batten J
AD  - Department of Pathology, Harvard Medical School, Massachusetts General Hospital, 
      Boston, Massachusetts.
FAU - Vernovsky, Kathy
AU  - Vernovsky K
AD  - Department of Pathology, Harvard Medical School, Massachusetts General Hospital, 
      Boston, Massachusetts.
FAU - Sweeney, Brenda
AU  - Sweeney B
AD  - Department of Pathology, Harvard Medical School, Massachusetts General Hospital, 
      Boston, Massachusetts.
FAU - Arpin, Ronald N
AU  - Arpin RN
AD  - Department of Pathology, Harvard Medical School, Massachusetts General Hospital, 
      Boston, Massachusetts.
FAU - Brugge, William R
AU  - Brugge WR
AD  - Department of Medicine, Harvard Medical School, Massachusetts General Hospital, 
      Boston, Massachusetts; Department of Gastroenterology, Harvard Medical School, 
      Massachusetts General Hospital, Boston, Massachusetts.
FAU - Forcione, David G
AU  - Forcione DG
AD  - Department of Medicine, Harvard Medical School, Massachusetts General Hospital, 
      Boston, Massachusetts; Department of Gastroenterology, Harvard Medical School, 
      Massachusetts General Hospital, Boston, Massachusetts.
FAU - Pitman, Martha B
AU  - Pitman MB
AD  - Department of Pathology, Harvard Medical School, Massachusetts General Hospital, 
      Boston, Massachusetts. Electronic address: mpitman@partners.org.
FAU - Iafrate, A John
AU  - Iafrate AJ
AD  - Department of Pathology, Harvard Medical School, Massachusetts General Hospital, 
      Boston, Massachusetts. Electronic address: aiafrate@partners.org.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151118
PL  - United States
TA  - J Mol Diagn
JT  - The Journal of molecular diagnostics : JMD
JID - 100893612
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (KRAS protein, human)
RN  - 0 (SMAD4 protein, human)
RN  - 0 (Smad4 Protein)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Base Sequence
MH  - Bile Ducts
MH  - Biliary Tract/cytology/pathology
MH  - Biliary Tract Neoplasms/*diagnosis/genetics
MH  - Cholangiopancreatography, Endoscopic Retrograde/methods
MH  - Cyclin-Dependent Kinase Inhibitor p16/genetics
MH  - Cytodiagnosis/*methods
MH  - False Negative Reactions
MH  - Female
MH  - High-Throughput Nucleotide Sequencing/*methods
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Male
MH  - Middle Aged
MH  - Pancreas/cytology/pathology
MH  - Pancreatic Neoplasms/*diagnosis/genetics
MH  - Proto-Oncogene Proteins p21(ras)/genetics
MH  - Sequence Analysis, DNA/methods
MH  - Smad4 Protein/genetics
MH  - Tumor Suppressor Protein p53/genetics
MH  - Young Adult
EDAT- 2015/11/26 06:00
MHDA- 2016/10/01 06:00
CRDT- 2015/11/25 06:00
PHST- 2015/02/18 00:00 [received]
PHST- 2015/07/24 00:00 [revised]
PHST- 2015/08/14 00:00 [accepted]
PHST- 2015/11/25 06:00 [entrez]
PHST- 2015/11/26 06:00 [pubmed]
PHST- 2016/10/01 06:00 [medline]
AID - S1525-1578(15)00222-6 [pii]
AID - 10.1016/j.jmoldx.2015.08.002 [doi]
PST - ppublish
SO  - J Mol Diagn. 2016 Jan;18(1):124-30. doi: 10.1016/j.jmoldx.2015.08.002. Epub 2015 
      Nov 18.