Molecular and Clinicopathologic Characterization of Intravenous Leiomyomatosis
Ordulu, Zehra (Massachusetts General Hospital (Boston))
Chai, Hongyan (Department of Genetics, Yale University School of Medicine; New Haven, CT)
Peng, Gang (Department of Biostatistics, Yale School of Public Health, New Haven, CT)
McDonald, Anna G. (Department of Pathology, Wake Forest Baptist Medical Center, Winston Salem, NC)
De Nictolis, Michele (Department of Pathology, San Salvatore Hospital, Pesaro, Italy)
Garcia-Fernandez, Eugenia (Hospital Universitario La Paz (Madrid))
Hardisson, David (Hospital Universitario La Paz (Madrid))
Prat, Jaime (Institut d'Investigació Biomèdica Sant Pau)
Li, Peining (Department of Genetics, Yale University School of Medicine; New Haven, CT)
Hui, Pei (Department of Pathology, Yale University School of Medicine; New Haven, CT)
Oliva, Esther (Massachusetts General Hospital (Boston))
Buza, Natalia (Department of Pathology, Yale University School of Medicine; New Haven, CT)

Fecha:	2020
Resumen:	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 non-neoplastic 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 3 molecular groups: Group 1 (29%) and 2 (18%) with associated del(22q) and group 3 (18%) with del(10q). The remaining IVL had non-specific 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.
Derechos:	Tots els drets reservats.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió acceptada per publicar
Materia:	Intravenous leiomyomatosis ; IVL ; Cellular ; Vascular ; Hyaline ; Angioleiomyoma ; Microarray ; Acgh ; Molecular ; Genetics ; 1p ; 1q ; 13q ; 22q ; 10q ; 14q ; Der(14) ; 8p ; 8q ; HMGA2 ; RB ; Cyclin D1 ; P16 ; Phosphorylated Rb ; SOX10 ; SDHB ; CAIX
Publicado en:	Modern Pathology, Vol. 33 (april 2020) , p. 1844-1860, ISSN 1530-0285

DOI: 10.1038/s41379-020-0546-8
PMID: 32341498

26 p, 1.8 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut de Recerca Sant Pau
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