NUT Is a Specific Immunohistochemical Marker for the Diagnosis of YAP1-NUTM1-rearranged Cutaneous Poroid Neoplasms.
Adaptor Proteins, Signal Transducing
/ genetics
Biomarkers, Tumor
/ analysis
Eccrine Porocarcinoma
/ diagnosis
Humans
Immunohistochemistry
Neoplasm Proteins
/ analysis
Nuclear Proteins
/ analysis
Oncogene Proteins, Fusion
Poroma
/ diagnosis
Sweat Gland Neoplasms
/ diagnosis
Transcription Factors
/ genetics
YAP-Signaling Proteins
Journal
The American journal of surgical pathology
ISSN: 1532-0979
Titre abrégé: Am J Surg Pathol
Pays: United States
ID NLM: 7707904
Informations de publication
Date de publication:
01 09 2021
01 09 2021
Historique:
pubmed:
20
3
2021
medline:
25
9
2021
entrez:
19
3
2021
Statut:
ppublish
Résumé
YAP1-NUTM1 fusion transcripts have been recently reported in poroma and porocarcinoma. NUTM1 translocation can be screened by nuclear protein in testis (NUT) immunohistochemistry in various malignancies, but its diagnostic performance has not been thoroughly validated on a large cohort of cutaneous epithelial neoplasms. We have evaluated NUT immunohistochemical expression in a large cohort encompassing 835 cases of various cutaneous epidermal or adnexal epithelial neoplasms. NUT expression was specific to eccrine poromas and porocarcinoma, with 32% of cases showing NUT expression. All other cutaneous tumors tested lacked NUT expression, including mimickers such as seborrheic keratosis, Bowen disease, basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, nodular hidradenoma, and all other adnexal tumors tested. Remarkably, NUT expression was more frequent in a distinct morphologic subgroup. Indeed, 93% of poroid hidradenoma (dermal/subcutaneous nodular poroma, 13/14) and 80% of poroid hidradenocarcinoma cases (malignant poroid hidradenoma, 4/5) showed NUT expression, in contrast to 17% and 11% of classic poroma (4/23) and porocarcinoma cases (4/35), respectively. RNA sequencing of 12 NUT-positive neoplasms further confirmed the presence of a YAP1-NUTM1 fusion transcript in all cases, and also an EMC7-NUTM1 gene fusion in a single case. In the setting of a cutaneous adnexal neoplasm, nuclear expression of NUT accurately and specifically diagnosed a specific subgroup of benign and malignant poroid tumors, all associated with a NUTM1 fusion, which frequently harbored a poroid hidradenoma morphology.
Identifiants
pubmed: 33739783
pii: 00000478-202109000-00007
doi: 10.1097/PAS.0000000000001693
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Biomarkers, Tumor
0
NUTM1 protein, human
0
Neoplasm Proteins
0
Nuclear Proteins
0
Oncogene Proteins, Fusion
0
Transcription Factors
0
YAP-Signaling Proteins
0
YAP1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1221-1227Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
Références
World Health Organization (WHO) In: Elder DE, Massi D, Scolyer RA, Willemze R, eds. WHO Classification of Skin Tumours, 4th ed. Lyon, France: International Agency for Research on Cancer; 2018:3p164.
Battistella M, Langbein L, Peltre B, et al. From hidroacanthoma simplex to poroid hidradenoma: clinicopathologic and immunohistochemic study of poroid neoplasms and reappraisal of their histogenesis. Am J Dermatopathol. 2010;32:459–468.
Goh SGN, Dayrit JF, Calonje E. Sarcomatoid eccrine porocarcinoma: report of two cases and a review of the literature. J Cutan Pathol. 2007;34:55–60.
Mahomed F, Blok J, Grayson W. The squamous variant of eccrine porocarcinoma: a clinicopathological study of 21 cases. J Clin Pathol. 2008;61:361–365.
Kazakov DV, Kutzner H, Spagnolo DV, et al. Sebaceous differentiation in poroid neoplasms: report of 11 cases, including a case of metaplastic carcinoma associated with apocrine poroma (sarcomatoid apocrine porocarcinoma). Am J Dermatopathol. 2008;30:21–26.
Requena L, Sarasa JL, Piqué E, et al. Clear-cell porocarcinoma: another cutaneous marker of diabetes mellitus. Am J Dermatopathol. 1997;19:540–544.
Miura K, Akashi T, Namiki T, et al. Engrailed homeobox 1 and cytokeratin 19 are independent diagnostic markers of eccrine porocarcinoma and distinguish it from squamous cell carcinoma. Am J Clin Pathol. 2020;154:499–509.
Claudy AL, Garcier F, Kanitakis J. Eccrine porocarcinoma. Ultrastructural and immunological study. J Dermatol. 1984;11:282–286.
Demirkesen C, Tüzüner N, Mat C, et al. Clinicopathologic evaluation of nodular cutaneous lesions of Behçet syndrome. Am J Clin Pathol. 2001;116:341–346.
Aslan F, Demirkesen C, Cağatay P, et al. Expression of cytokeratin subtypes in intraepidermal malignancies: a guide for differentiation. J Cutan Pathol. 2006;33:531–538.
Sekine S, Kiyono T, Ryo E, et al. Recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poroma and porocarcinoma. J Clin Invest. 2019;129:3827–3832.
Russell-Goldman E, Hornick JL, Hanna J. Utility of YAP1 and NUT immunohistochemistry in the diagnosis of porocarcinoma. J Cutan Pathol. 2021. [Epub ahead print].
Haack H, Johnson LA, Fry CJ, et al. Diagnosis of NUT midline carcinoma using a NUT-specific monoclonal antibody. Am J Surg Pathol. 2009;33:984–991.
Shiota H, Barral S, Buchou T, et al. Nut directs p300-dependent, genome-wide H4 hyperacetylation in Male germ cells. Cell Rep. 2018;24:3477.e6–3487.e6.
French CA, Miyoshi I, Kubonishi I, et al. BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. Cancer Res. 2003;63:304–307.
Huang QW, He LJ, Zheng S, et al. An overview of molecular mechanism, clinicopathological factors, and treatment in NUT carcinoma. Biomed Res Int. 2019;2019:1018439.
French CA, Ramirez CL, Kolmakova J, et al. BRD-NUT oncoproteins: a family of closely related nuclear proteins that block epithelial differentiation and maintain the growth of carcinoma cells. Oncogene. 2008;27:2237–2242.
Stelow EB, French CA. Carcinomas of the upper aerodigestive tract with rearrangement of the nuclear protein of the testis (NUT) gene (NUT midline carcinomas). Adv Anat Pathol. 2009;16:92–96.
Minato H, Kobayashi E, Nakada S, et al. Sinonasal NUT carcinoma: clinicopathological and cytogenetic analysis with autopsy findings. Hum Pathol. 2018;71:157–165.
McEvoy CR, Fox SB, Prall OWJ. Emerging entities in NUTM1-rearranged neoplasms. Genes Chromosomes Cancer. 2020;59:375–385.
Stevens TM, Morlote D, Xiu J, et al. NUTM1-rearranged neoplasia: a multi-institution experience yields novel fusion partners and expands the histologic spectrum. Mod Pathol. 2019;32:764–773.
Hormann FM, Hoogkamer AQ, Beverloo HB, et al. NUTM1 is a recurrent fusion gene partner in B-cell precursor acute lymphoblastic leukemia associated with increased expression of genes on chromosome band 10p12.31-12.2. Haematologica. 2019;104:e455–e459.
Agaimy A, Tögel L, Haller F, et al. YAP1-NUTM1 gene fusion in porocarcinoma of the external auditory canal. Head Neck Pathol. 2020;14:982–990.
Robson A, Greene J, Ansari N, et al. Eccrine porocarcinoma (malignant eccrine poroma): a clinicopathologic study of 69 cases. Am J Surg Pathol. 2001;25:710–720.
Zahn J, Chan MP, Wang G, et al. Altered Rb, p16, and p53 expression is specific for porocarcinoma relative to poroma. J Cutan Pathol. 2019;46:659–664.
Requena L, Sánchez M. Poroid hidradenoma: a light microscopic and immunohistochemical study. Cutis. 1992;50:43–46.
Kuma Y, Yamada Y, Yamamoto H, et al. A novel fusion gene CRTC3-MAML2 in hidradenoma: histopathological significance. Hum Pathol. 2017;70:55–61.