Genetic and immunohistochemical profiling of small cell and large cell neuroendocrine carcinomas of the breast.

Breast Neoplasms / genetics Carcinoma, Intraductal, Noninfiltrating Carcinoma, Large Cell / genetics Carcinoma, Neuroendocrine / pathology Carrier Proteins Cell Cycle Proteins Class I Phosphatidylinositol 3-Kinases / metabolism Female Humans Neuroendocrine Tumors / pathology Proto-Oncogene Proteins / metabolism Tumor Suppressor Protein p53 / genetics

Journal

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
ISSN: 1530-0285
Titre abrégé: Mod Pathol
Pays: United States
ID NLM: 8806605

Informations de publication

Date de publication:
10 2022
Historique:
received: 05 01 2022
accepted: 14 04 2022
revised: 13 04 2022
pubmed: 20 5 2022
medline: 30 9 2022
entrez: 19 5 2022
Statut: ppublish

Résumé

Neuroendocrine carcinomas (NEC) of the breast are exceedingly rare tumors, which are classified in the WHO system as small cell (SCNEC) and large cell (LCNEC) carcinoma based on indistinguishable features from their lung counterparts. In contrast to lung and enteropancreatic NEC, the genomics of breast NEC have not been well-characterized. In this study, we examined the clinicopathologic, immunohistochemical, and genetic features of 13 breast NEC (7 SCNEC, 4 LCNEC, 2 NEC with ambiguous small versus large cell morphology [ANEC]). Co-alterations of TP53 and RB1 were identified in 86% (6/7) SCNEC, 100% (2/2) ANEC, and 50% (2/4) LCNEC. The one SCNEC without TP53/RB1 alteration had other p53 pathway aberrations (MDM2 and MDM4 amplification) and was immunohistochemically RB negative. PIK3CA/PTEN pathway alterations and ZNF703 amplifications were each identified in 46% (6/13) NEC. Two tumors (1 SCNEC, 1 LCNEC) were CDH1 mutated. By immunohistochemistry, 100% SCNEC (6/6) and ANEC (2/2) and 50% (2/4) LCNEC (83% NEC) showed RB loss, compared to 0% (0/8) grade 3 neuroendocrine tumors (NET) (p < 0.001) and 38% (36/95) grade 3 invasive ductal carcinomas of no special type (IDC-NST) (p = 0.004). NEC were also more often p53 aberrant (60% vs 0%, p = 0.013), ER negative (69% vs 0%, p = 0.005), and GATA3 negative (67% vs 0%, p = 0.013) than grade 3 NET. Two mixed NEC had IDC-NST components, and 69% (9/13) of tumors were associated with carcinoma in situ (6 neuroendocrine DCIS, 2 non-neuroendocrine DCIS, 1 non-neuroendocrine LCIS). NEC and IDC-NST components of mixed tumors were clonally related and immunophenotypically distinct, lacking ER and GATA3 expression in NEC relative to IDC-NST, with RB loss only in NEC of one ANEC. The findings provide insight into the pathogenesis of breast NEC, underscore their classification as a distinct tumor type, and highlight genetic similarities to extramammary NEC, including highly prevalent p53/RB pathway aberrations in SCNEC.

Identifiants

DOI: 10.1038/s41379-022-01090-y PMID: 35590107 PMC: PMC9514991
pubmed: 35590107
doi: 10.1038/s41379-022-01090-y
pii: S0893-3952(22)00250-2
pmc: PMC9514991
doi:

Substances chimiques

Carrier Proteins 0
Cell Cycle Proteins 0
MDM4 protein, human 0
Proto-Oncogene Proteins 0
Tumor Suppressor Protein p53 0
ZNF703 protein, human 0
Class I Phosphatidylinositol 3-Kinases EC 2.7.1.137

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1349-1361

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© 2022. The Author(s).

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Auteurs

Gregory R Bean (GR)

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
ORCID: 0000-0003-2866-8283

Saleh Najjar (S)

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.

Sandra J Shin (SJ)

Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY, USA.

Elizabeth M Hosfield (EM)

Department of Pathology, Kaiser Permanente San Francisco Medical Center, San Francisco, CA, USA.

Jennifer L Caswell-Jin (JL)

Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA, USA.

Anatoly Urisman (A)

Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
ORCID: 0000-0001-8364-5303

Kirk D Jones (KD)

Department of Pathology, University of California San Francisco, San Francisco, CA, USA.

Yunn-Yi Chen (YY)

Department of Pathology, University of California San Francisco, San Francisco, CA, USA.

Gregor Krings (G)

Department of Pathology, University of California San Francisco, San Francisco, CA, USA. gregor.krings@ucsf.edu.

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Classifications MeSH

Recherchemedicale.com › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Maladies du sein › Tumeurs du sein › Genetic and immunohistochemical profiling of...
Recherchemedicale.com › Tumeurs › Tumeurs par type histologique › Tumeurs épithéliales épidermoïdes et glandulaires › Tumeurs canalaires, lobulaires et médullaires › Carcinome intracanalaire non infiltrant › Genetic and immunohistochemical profiling of...
Recherchemedicale.com › Tumeurs › Tumeurs par type histologique › Tumeurs épithéliales épidermoïdes et glandulaires › Carcinomes › Carcinome à grandes cellules › Genetic and immunohistochemical profiling of...
Recherchemedicale.com › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroendocrines › Carcinome neuroendocrine › Genetic and immunohistochemical profiling of...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines de transport › Genetic and immunohistochemical profiling of...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines du cycle cellulaire › Genetic and immunohistochemical profiling of...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Phosphatidylinositol 3-kinases › Phosphatidylinositol-4-phosphate 3-kinase › Phosphatidylinositol 3-kinases de classe I › Genetic and immunohistochemical profiling of...
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Recherchemedicale.com › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroendocrines › Genetic and immunohistochemical profiling of...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines proto-oncogènes › Genetic and immunohistochemical profiling of...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Phosphoprotéines › Protéine p53 suppresseur de tumeur › Genetic and immunohistochemical profiling of...