Stains & molecular markers
NUTM1
Copyright: 2003-2021, PathologyOutlines.com, Inc.
PubMed Search: NUTM1
NUTM1
Author: Brendan C. Dickson, M.D., M.Sc.
Editor-in-Chief: Debra L. Zynger, M.D.
Topic Completed: 2 May 2018
Minor changes: 9 October 2020
Copyright: 2003-2021, PathologyOutlines.com, Inc.
PubMed Search: NUTM1
Table of Contents
Definition / general | Essential features | Pathophysiology | Interpretation | Uses by pathologists | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative staining - normal | Negative staining - disease | Board review style question #1 | Board review style answer #1Cite this page: Dickson, B. NUTM1. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsnutm1.html. Accessed April 14th, 2021.
Definition / general
- NUTM1 (NUT midline carcinoma family member 1) encodes the NUT family member 1 protein (also known as: nuclear protein in testis, FAM22H and NUT)
- NUT carcinoma is characterized by the fusion of NUTM1 with another gene (e.g., BRD4); resulting oncoprotein causes tumor growth (Genes Dev 2015;29:1507, Proc Natl Acad Sci U S A 2017;114:E4184)
- Translocations involving NUTM1 can be detected by immunohistochemistry for NUT
Essential features
- Diagnosis of NUT carcinoma is predicated on immunohistochemical demonstration of nuclear NUT staining (or molecular confirmation of NUTM1 rearrangement)
- NUT is expressed in a subset of germ cell tumors (Am J Surg Pathol 2009;33:984)
- Normal overexpression of this biomarker is limited to testicular and ovarian germ cells (Cancer Res 2003;63:304, Am J Surg Pathol 2009;33:984)
Pathophysiology
- Function of the NUT protein remains poorly understood
- NUT carcinoma is characterized by the fusion of NUTM1 with another gene (e.g., BRD4, BRD3 or NSD3, among others); these proteins bind acetylated chromatin; these domains result in dysregulated transcription of genes, including cMYC and TP63, which promote tumor growth (Genes Dev 2015;29:1507, Proc Natl Acad Sci U S A 2017;114:E4184)
Interpretation
- In NUT carcinoma staining is nuclear, with a speckled distribution (> 90% of cells are generally positive; the reported sensitivity is 87% and the specificity is 100% (clone: C52, Am J Surg Pathol 2009;33:984)
- In germ cell tumors staining is nuclear, with an even / uniform distribution and often only focal (Am J Surg Pathol 2009;33:984, Histopathology 2014;65:35, Pathology 2015;47:118)
Uses by pathologists
- NUT is a biomarker for NUT carcinoma (Am J Surg Pathol 2009;33:984) and neoplasms harboring NUTM1 fusion genes (Cell 2016;164:1060, Am J Surg Pathol 2018;42:636); presence of staining confirms the diagnosis and excludes potential mimics
- NUT is variably expressed among germ cell tumors, including: dysgerminoma (64 - 93%), embryonal carcinoma (0 - 9%), immature teratoma (75%), seminoma (6 - 74%), spermatocytic seminoma (100%) and yolk sac tumor (7 - 100%) (Am J Surg Pathol 2009;33:984, Histopathology 2014;65:35, Pathology 2015;47:118) However, in this context and in the absence of broader panel of immunohistochemical markers, NUT alone is of limited diagnostic value
Microscopic (histologic) images
Contributed by Brendan Dickson, M.D.
NUT carcinoma arising in the sinonasal tract: H&E
NUT carcinoma arising in the sinonasal tract: IHC
Positive staining - normal
- Testis: germ cells (Am J Surg Pathol 2009;33:984)
- Ovary: oocytes (weak) (Am J Surg Pathol 2009;33:984)
Positive staining - disease
- NUT carcinoma (Am J Surg Pathol 2009;33:984)
- CNS: PNET with CIC-NUTM1 fusions (Cell 2016;164:1060)
- NUT associate tumors arising in the soft tissue and viscera (Am J Surg Pathol 2018;42:636)
- Germ cell tumors: spermatocytic tumor, other germ cell tumor staining often focal or weak (Am J Surg Pathol 2009;33:984, Histopathology 2014;65:35, Pathology 2015;47:118)
Negative staining - normal
- Breast
- Large intestine
- Liver (minority of cases may contain cytoplasmic and nuclear blush)
- Lung
- Prostate
- Thymus
- Tonsil (Am J Surg Pathol 2009;33:984)
Negative staining - disease
- Adenocarcinoma, NOS
- Ewing sarcoma
- Nasopharyngeal carcinoma
- Neuroblastoma
- Renal cell carcinoma
- Rhabdomyosarcoma
- Rhabdoid tumor
- Serous carcinoma
- Sinonasal undifferentiated carcinoma
- Small cell carcinoma
- Squamous cell carcinoma, NOS
- Urothelial carcinoma (Am J Surg Pathol 2009;33:984)
Board review style question #1
- A mediastinal mass is biopsied, which shows a morphologically undifferentiated carcinoma. Which of the following staining patterns would be most consistent with classification as NUT carcinoma?
- Nuclear expression in > 90% of cells with a speckled pattern
- Nuclear expression in > 90% of cells with an even / uniform pattern
- Cytoplasmic expression in < 90% of cells with a speckled pattern
- Cytoplasmic expression in < 90% of cells with an even / uniform pattern
Board review style answer #1
A. Nuclear expression in > 90% of cells with a speckled pattern. In NUT carcinoma most tumor cells are positive for this biomarker, which is expressed in the nucleus with a speckled distribution. In contrast, germ cell tumors often have only focal tumor staining, which is expressed in the nucleus with an even/uniform distribution.
