PMID- 19363441
OWN - NLM
STAT- MEDLINE
DCOM- 20100202
LR  - 20220310
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Print)
IS  - 0147-5185 (Linking)
VI  - 33
IP  - 7
DP  - 2009 Jul
TI  - Diagnosis of NUT midline carcinoma using a NUT-specific monoclonal antibody.
PG  - 984-91
LID - 10.1097/PAS.0b013e318198d666 [doi]
AB  - NUT midline carcinoma (NMC) is a uniformly lethal malignancy that is defined by 
      rearrangement of the nuclear protein in testis (NUT) gene on chromosome 15q14. 
      NMCs are morphologically indistinguishable from other poorly differentiated 
      carcinomas, and the diagnosis is usually made currently by fluorescence in situ 
      hybridization (FISH). As normal NUT expression is confined to testis and ovary, 
      we reasoned that an immunohistochemical (IHC) stain for NUT would be useful in 
      diagnosing NMC. To this end, we raised a highly specific rabbit monoclonal 
      antibody, C52, against a recombinant NUT polypeptide, and developed an IHC 
      staining protocol. The sensitivity and specificity of C52 staining was evaluated 
      in a panel of 1068 tissues, predominantly diverse types of carcinomas (n=906), 
      including 30 NMCs. Split-apart FISH for NUT rearrangement was used as a "gold 
      standard" diagnostic test for NMC. C52 immunoreactivity among carcinomas was 
      confined to NMCs. IHC staining had a sensitivity of 87%, a specificity of 100%, a 
      negative predictive value of 99%, and a positive predictive value of 100%. Two 
      new cases of NMC containing BRD4-NUT fusions were detected by C52 IHC, but missed 
      by conventional FISH. In both instances, these tumors contained cryptic BRD4-NUT 
      rearrangements, as confirmed by FISH using a refined set of probes. Some germ 
      cell tumors, including 64% of dysgerminomas, showed weak NUT immunoreactivity, 
      consistent with the expression of NUT in normal germ cells. We conclude that IHC 
      staining with the C52 monoclonal antibody is a highly sensitive and specific test 
      that reliably distinguishes NMC from other forms of carcinoma. The NUT antibody 
      is being prepared for commercial release and will be available in the near 
      future.
FAU - Haack, Herbert
AU  - Haack H
AD  - Cell Signaling Technology Inc., Danvers, MA, USA.
FAU - Johnson, Laura A
AU  - Johnson LA
FAU - Fry, Christopher J
AU  - Fry CJ
FAU - Crosby, Katherine
AU  - Crosby K
FAU - Polakiewicz, Roberto D
AU  - Polakiewicz RD
FAU - Stelow, Edward B
AU  - Stelow EB
FAU - Hong, Seung-Mo
AU  - Hong SM
FAU - Schwartz, Brian E
AU  - Schwartz BE
FAU - Cameron, Michael J
AU  - Cameron MJ
FAU - Rubin, Mark A
AU  - Rubin MA
FAU - Chang, Martin C
AU  - Chang MC
FAU - Aster, Jon C
AU  - Aster JC
FAU - French, Christopher A
AU  - French CA
LA  - eng
GR  - R01 CA124633/CA/NCI NIH HHS/United States
GR  - R01 CA124633-02/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (BRD4-NUT fusion oncogene protein, human)
RN  - 0 (NUTM1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Oncogene Proteins, Fusion)
SB  - IM
MH  - Animals
MH  - *Antibodies, Monoclonal
MH  - Antibody Specificity
MH  - Carcinoma/*diagnosis/genetics
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Neoplasm Proteins
MH  - Nuclear Proteins/genetics/immunology
MH  - Oncogene Proteins/genetics/immunology
MH  - Oncogene Proteins, Fusion
MH  - Rabbits
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sensitivity and Specificity
PMC - PMC2783402
MID - NIHMS87267
EDAT- 2009/04/14 09:00
MHDA- 2010/02/03 06:00
PMCR- 2010/07/01
CRDT- 2009/04/14 09:00
PHST- 2009/04/14 09:00 [entrez]
PHST- 2009/04/14 09:00 [pubmed]
PHST- 2010/02/03 06:00 [medline]
PHST- 2010/07/01 00:00 [pmc-release]
AID - 10.1097/PAS.0b013e318198d666 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2009 Jul;33(7):984-91. doi: 10.1097/PAS.0b013e318198d666.