Diagnosis of NUT midline carcinoma using a NUT-specific monoclonal antibody.

Cell Signaling Technology Inc., Danvers, MA, USA.
The American journal of surgical pathology (Impact Factor: 4.59). 05/2009; 33(7):984-91. DOI: 10.1097/PAS.0b013e318198d666
Source: PubMed

ABSTRACT 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.


Available from: Seung-Mo Hong, Jan 14, 2014
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    ABSTRACT: NUT Midline carcinoma (NMC) is a rare and invariably fatal poorly differentiated carcinoma characterized by chromosomal rearrangement involving the nuclear protein of the testis (NUT) gene. Current approaches do not provide durable response. We report a case of widely metastatic NMC in a 17-year-old female who, following an initial response to combination chemotherapy developed rapid disease progression. Treatment with vorinostat, a histone deacetylase inhibitor (HDACi) resulted in an objective response, yet she died in less than one year from initial diagnosis. This report shows a potentially promising activity of HDACi in the treatment of NMC that needs further exploration. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 01/2015; DOI:10.1002/pbc.25350 · 2.56 Impact Factor
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    ABSTRACT: Background. Nuclear protein in testis (NUT) midline carcinoma (NMC) is a very rare and aggressive malignancy. In more than two-thirds of these NMC cases, a fusion between NUT and BRD4 or BRD3 has been documented; other variants are rare. The cytology of NMC itself has been sparsely documented and that of variant NMC has never been reported. Case Presentation. A 36-year-old woman was admitted because of a rapidly progressing lung tumor with metastases to the breast and bone. We recently reported this patient as the first case of a variant NMC of the lung harboring an NSD3-NUT fusion, based on immunohistochemical and genetic analyses. Cytological material was available for the present review. A highly cellular smear contained a predominantly noncohesive pattern of monomorphic cells with diameters 2-2.5 times greater than those of small lymphocytes, with a round-to-oval nucleus, slightly irregular nuclear contours, variably prominent nucleoli, scant cytoplasm, and identifiable mitotic figures. Foci of stratification and overt pearl formation, including a dyskeratocyte, were occasionally observed. The necrotic background contained naked nuclei, karyorrhectic debris, apoptotic cells, and macrophages phagocytizing karyorrhectic debris; nuclear crushing was noted. Conclusion. The cytological features of a variant NMC of the lung are described for the first time.
    01/2015; 2015:572951. DOI:10.1155/2015/572951
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    ABSTRACT: Nuclear protein of the testis (NUT) midline carcinoma (NMC) is an uncommon, relatively recently characterized carcinoma, which is defined by NUT gene rearrangements. We are reporting a case of NMC in a 38-year-old female who presented with pleural effusion and bilateral ovarian masses. We also discuss some of the difficulties encountered by the practicing pathologist in reaching the diagnosis and the role of ancillary studies. Immunohistochemical staining using a commercially available monoclonal antibody showing nuclear expression of the NUT protein is diagnostic of NMC. Dual-color split-apart fluorescence in situ hybridization (FISH) or reverse transcription polymerase chain reaction (RT-PCR) can be used to characterize the fusion gene, whether BRD4-NUT or BRD3-NUT, or NUT-variant.
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