Stains
NUTM1
Copyright: 2003-2019, PathologyOutlines.com, Inc.
PubMed Search: NUTM1
NUTM1
Author: Brendan C. Dickson, M.D., M.Sc.
Deputy Editor-in-Chief: Debra Zynger, M.D.
Topic Completed: 2 May 2018
Minor changes: 5 February 2019
Copyright: 2003-2019, 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 answer #1Cite this page: Dickson, B. NUTM1. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsnutm1.html. Accessed June 7th, 2020.
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
Images hosted on PathOut server:
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 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.
