Diagnosis of NUT Midline Carcinoma Using a NUT-specific Monoclonal Antibody
Top Cited Papers
- 1 July 2009
- journal article
- research article
- Published by Wolters Kluwer Health in The American Journal of Surgical Pathology
- Vol. 33 (7), 984-991
- https://doi.org/10.1097/pas.0b013e318198d666
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.Keywords
This publication has 9 references indexed in Scilit:
- Demystified molecular pathology of NUT midline carcinomasJournal of Clinical Pathology, 2008
- NUT Rearrangement in Undifferentiated Carcinomas of the Upper Aerodigestive TractThe American Journal of Surgical Pathology, 2008
- BRD–NUT oncoproteins: a family of closely related nuclear proteins that block epithelial differentiation and maintain the growth of carcinoma cellsOncogene, 2007
- Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancerNature, 2007
- Successful treatment of a child with t(15;19)‐positive tumorPediatric Blood & Cancer, 2006
- Midline Carcinoma of Children and Young Adults With NUT RearrangementJournal of Clinical Oncology, 2004
- Translocation (11;15;19): a Highly Specific Chromosome Rearrangement Associated With Poorly Differentiated Thymic Carcinoma in Young PatientsAmerican Journal of Clinical Oncology, 2003
- BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma.2003
- BRD4 Bromodomain Gene Rearrangement in Aggressive Carcinoma with Translocation t(15;19)The American Journal of Pathology, 2001