Molecular and clinicopathologic characterization of intravenous leiomyomatosis.
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:
09 2020
09 2020
Historique:
received:
19
01
2020
accepted:
06
04
2020
revised:
06
04
2020
pubmed:
29
4
2020
medline:
21
7
2021
entrez:
29
4
2020
Statut:
ppublish
Résumé
Intravenous leiomyomatosis (IVL) is an unusual uterine smooth muscle proliferation that can be associated with aggressive clinical behavior despite a histologically benign appearance. It has some overlapping molecular characteristics with both uterine leiomyoma and leiomyosarcoma based on limited genetic data. In this study, we assessed the clinical and morphological characteristics of 28 IVL and their correlation with molecular features and protein expression, using array comparative genomic hybridization (aCGH) and Cyclin D1, p16, phosphorylated-Rb, SMARCB1, SOX10, CAIX, SDHB and FH immunohistochemistry. The most common morphologies were cellular (n = 15), usual (n = 11), and vascular (n = 5; including 3 cellular IVL showing both vascular and cellular features). Among the immunohistochemical findings, the most striking was that all IVL showed differential expression of either p16 or Cyclin D1 in comparison to surrounding nonneoplastic tissue. Cytoplasmic phosphorylated-Rb was present in all but one IVL with hyalinization. SMARCB1, FH, and SDHB were retained; S0X10 and CAIX were not expressed. The most common genetic alterations involved 1p (39%), 22q (36%), 2q (29%), 1q (25%), 13q (21%), and 14q (21%). Hierarchical clustering analysis of recurrent aberrations revealed three molecular groups: Groups 1 (29%) and 2 (18%) with associated del(22q), and Group 3 (18%) with del(10q). The remaining IVL had nonspecific or no alterations by aCGH. Genomic index scores were calculated for all cases and showed no significant difference between the 14 IVL associated with aggressive clinical behavior (extrauterine extension or recurrence) and those without (median scores 5.15 vs 3.5). Among the 5 IVL associated with recurrence, 4 had a vascular morphology and 3 had alterations of 8q. Recurrent chromosome alterations detected herein overlap with those observed in the spectrum of uterine smooth muscle tumors and involve genes implicated in mesenchymal tumors at different sites with distinct morphological features.
Identifiants
pubmed: 32341498
doi: 10.1038/s41379-020-0546-8
pii: S0893-3952(22)00713-X
pmc: PMC7483566
mid: NIHMS1582977
doi:
Substances chimiques
CDKN2A protein, human
0
Cyclin-Dependent Kinase Inhibitor p16
0
Cyclin D1
136601-57-5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1844-1860Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR002541
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)
ID : UL 1TR002541
Pays : International
Organisme : U.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute (National Cancer Institute Division of Cancer Epidemiology and Genetics)
ID : 5 P30 CA06516
Pays : International
Organisme : NCI NIH HHS
ID : P30 CA006516
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : 5 P30 CA06516
Pays : International
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