Endometrial neuroendocrine carcinoma and undifferentiated carcinoma are distinct entities with overlap in neuroendocrine marker expression.
BRG1
INI1
dedifferentiated cancer
neuroendocrine cancer
undifferentiated cancer
Journal
Histopathology
ISSN: 1365-2559
Titre abrégé: Histopathology
Pays: England
ID NLM: 7704136
Informations de publication
Date de publication:
Jul 2022
Jul 2022
Historique:
revised:
01
03
2022
received:
07
01
2022
accepted:
02
03
2022
pubmed:
9
4
2022
medline:
22
6
2022
entrez:
8
4
2022
Statut:
ppublish
Résumé
Dedifferentiated endometrial carcinomas (DDECs)/undifferentiated endometrial carcinomas (UDECs) frequently harbour genomic activation of switch/sucrose non-fermentable (SWI/SNF)-complex proteins, and can show histological overlap with neuroendocrine carcinoma (NEC). The aim of this study was to compare the extent of the expression of neuroendocrine markers, SWI/SNF proteins and mismatch repair (MMR) proteins in DDEC/UDEC and NEC. The extent of expression of synaptophysin, chromogranin, CD56, ARID1A, ARID1B, SMARCA4, SMARCB1 and MMR proteins was evaluated by immunohistochemistry on 44 SWI/SNF-deficient DDECs/UDECs and 15 NECs. Thirty-three of 44 (75%) DDECs/UDECs showed expression of at least one neuroendocrine marker, with 18 of 44 (41%) expressing two or more neuroendocrine markers, whereas all 15 NECs showed expression of at least one neuroendocrine marker, with 14 of 15 (93%) expressing two or more neuroendocrine markers. Neuroendocrine marker expression in DDECs/UDECs was typically focal when present, with average extents of 17%, 4% and 8% for synaptophysin, chromogranin and CD56 in the positive cases, respectively, in contrast to 73%, 40% and 62% in the positive NEC cases, respectively. All 15 NECs showed intact expression of SWI/SNF-complex proteins, except for one that showed isolated loss of ARID1A. Thirty-eight of 44 DDECs/UDECs were MMR-abnormal (34 with loss of MLH1 and PMS2, and four with loss of PMS2 alone), whereas all NECs retained MMR protein expression. Our study demonstrates frequent but typically focal neuroendocrine marker expression in SWI/SNF-deficient DDECs/UDECs, whereas NECs typically express two or more neuroendocrine markers, with diffuse expression of at least one marker. ARID1B, SMARCA4 and SMARCB1 immunohistochemistry can be used to aid in the differentiation between DDEC/UDEC and NEC.
Substances chimiques
Biomarkers, Tumor
0
Chromogranins
0
Nuclear Proteins
0
Synaptophysin
0
Transcription Factors
0
SMARCA4 protein, human
EC 3.6.1.-
Mismatch Repair Endonuclease PMS2
EC 3.6.1.3
DNA Helicases
EC 3.6.4.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
44-54Subventions
Organisme : Calgary Laboratory Services
ID : RS14513
Organisme : Cancer Research Society
Informations de copyright
© 2022 John Wiley & Sons Ltd.
Références
Palacios J, Ramalingam P, Lee CH. Undifferentiated and dedifferentiated carcinomas of the uterine corpus. In WHO Classification of Tumours Editorial Board ed. Female genital tumours. Lyon: IARC Press, 2020; 260-261.
Silva EG, Deavers MT, Bodurka DC, Malpica A. Association of low-grade endometrioid carcinoma of the uterus and ovary with undifferentiated carcinoma: a new type of dedifferentiated carcinoma? Int. J. Gynecol. Pathol. 2006; 25; 52-58.
Silva EG, Deavers MT, Malpica A. Undifferentiated carcinoma of the endometrium: a review. Pathology 2007; 39; 134-138.
Atienza-Amores M, Guerini-Rocco E, Soslow RA, Park KJ, Weigelt B. Small cell carcinoma of the gynecologic tract: a multifaceted spectrum of lesions. Gynecol. Oncol. 2014; 134; 410-418.
Karnezis AN, Hoang LN, Coatham M et al. Loss of switch/sucrose non-fermenting complex protein expression is associated with dedifferentiation in endometrial carcinomas. Mod. Pathol. 2016; 29; 302-314.
Coatham M, Li X, Karnezis AN et al. Concurrent ARID1A and ARID1B inactivation in endometrial and ovarian dedifferentiated carcinomas. Mod. Pathol. 2016; 29; 1586-1593.
Kobel M, Hoang LN, Tessier-Cloutier B et al. Undifferentiated endometrial carcinomas show frequent loss of core switch/sucrose nonfermentable complex proteins. Am. J. Surg. Pathol. 2018; 42; 76-83.
Kihara A, Amano Y, Matsubara D, Fukushima N, Fujiwara H, Niki T. BRG1, INI1, and ARID1B deficiency in endometrial carcinoma: a clinicopathologic and immunohistochemical analysis of a large series from a single institution. Am. J. Surg. Pathol. 2020; 44; 1712-1724.
Stewart CJ, Crook ML. SWI/SNF complex deficiency and mismatch repair protein expression in undifferentiated and dedifferentiated endometrial carcinoma. Pathology 2015; 47; 439-445.
Strehl JD, Wachter DL, Fiedler J et al. Pattern of SMARCB1 (INI1) and SMARCA4 (BRG1) in poorly differentiated endometrioid adenocarcinoma of the uterus: Analysis of a series with emphasis on a novel SMARCA4-deficient dedifferentiated rhabdoid variant. Ann. Diagn. Pathol. 2015; 19; 198-202.
Tessier-Cloutier B, Coatham M, Carey M et al. SWI/SNF-deficiency defines highly aggressive undifferentiated endometrial carcinoma. J. Pathol. Clin. Res. 2021; 7; 144-153.
Taraif SH, Deavers MT, Malpica A, Silva EG. The significance of neuroendocrine expression in undifferentiated carcinoma of the endometrium. Int. J. Gynecol. Pathol. 2009; 28; 142-147.
Tafe LJ, Garg K, Chew I, Tornos C, Soslow RA. Endometrial and ovarian carcinomas with undifferentiated components: clinically aggressive and frequently underrecognized neoplasms. Mod. Pathol. 2010; 23; 781-789.
Onder S, Taskin OC, Sen F et al. High expression of SALL4 and fascin, and loss of E-cadherin expression in undifferentiated/dedifferentiated carcinomas of the endometrium: an immunohistochemical and clinicopathologic study. Medicine (Baltimore) 2017; 96; e6248.
Espinosa I, De Leo A, D'Angelo E et al. Dedifferentiated endometrial carcinomas with neuroendocrine features: a clinicopathologic, immunohistochemical, and molecular genetic study. Hum. Pathol. 2018; 72; 100-106.
Howitt BE, Dong F, Vivero M et al. Molecular characterization of neuroendocrine carcinomas of the endometrium: representation in all 4 TCGA groups. Am. J. Surg. Pathol. 2020; 44; 1541-1548.
Karnezis AN, Wang Y, Ramos P et al. Dual loss of the SWI/SNF complex ATPases SMARCA4/BRG1 and SMARCA2/BRM is highly sensitive and specific for small cell carcinoma of the ovary, hypercalcemic type. J. Pathol. 2016; 238; 389-400.
Alvarado-Cabrero I, Howitt BE, Ganesan R et al. Small cell neuroendocrine carcinoma and large cell neuroendocrine carcinoma. In WHO Classification of Tumours Editorial Board ed. Female genital tumours. Lyon: IARC Press, 2020; 455-458.
Pocrnich CE, Ramalingam P, Euscher ED, Malpica A. Neuroendocrine carcinoma of the endometrium: a clinicopathologic study of 25 cases. Am. J. Surg. Pathol. 2016; 40; 577-586.
Mulvany NJ, Allen DG. Combined large cell neuroendocrine and endometrioid carcinoma of the endometrium. Int. J. Gynecol. Pathol. 2008; 27; 49-57.
Busca A, Parra-Herran C, Nofech-Mozes S et al. Undifferentiated endometrial carcinoma arising in the background of high-grade endometrial carcinoma-expanding the definition of dedifferentiated endometrial carcinoma. Histopathology 2020; 77; 769-780.
Moritz AW, Schlumbrecht MP, Nadji M, Pinto A. Expression of neuroendocrine markers in non-neuroendocrine endometrial carcinomas. Pathology 2019; 51; 369-374.
Tamura T, Jobo T, Watanabe J, Kanai T, Kuramoto H. Neuroendocrine features in poorly differentiated endometrioid adenocarcinomas of the endometrium. Int. J. Gynecol. Cancer 2006; 16; 821-826.