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PARP-1 expression as a prognostic factor in Desmoid-type fibromatosis

Desmoid-type fibromatoses (or desmoid tumors) are entities of intermediate biological potential and are locally invasive. Radical surgery, as state of the art therapy, is frequently limited by incomplete resections. Hormone modifying therapies are promising but further research is required. Poly Ade...

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Hauptverfasser: Bräutigam, Konstantin Benno (VerfasserIn) , Lindner, Judith Lea (VerfasserIn) , Budczies, Jan (VerfasserIn) , Pahl, Stefan (VerfasserIn) , Kunitz, Annegret (VerfasserIn) , Melcher, Ingo (VerfasserIn) , Wust, Peter (VerfasserIn) , Nebrig, Maxim (VerfasserIn) , Baur, Alexander (VerfasserIn) , Denkert, Carsten (VerfasserIn) , Pfitzner, Berit (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2020
In: Annals of diagnostic pathology
Year: 2019, Jahrgang: 44
ISSN:1532-8198
DOI:10.1016/j.anndiagpath.2019.151442
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.anndiagpath.2019.151442
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S1092913419303715
Volltext
Verfasserangaben:Konstantin Bräutigam, Judith Lindner, Jan Budczies, Stefan Pahl, Annegret Kunitz, Ingo Melcher, Peter Wust, Maxim Nebrig, Alexander Baur, Carsten Denkert, Berit Pfitzner
Beschreibung
Zusammenfassung:Desmoid-type fibromatoses (or desmoid tumors) are entities of intermediate biological potential and are locally invasive. Radical surgery, as state of the art therapy, is frequently limited by incomplete resections. Hormone modifying therapies are promising but further research is required. Poly Adenosine Diphosphate Ribose Polymerase-1 (PARP-1), a DNA repairing enzyme, might be a pathogenetic factor and could become a potential target for therapy as shown by the successful treatment of selected carcinomas and sarcomas by PARP-inhibition. In this study, we investigated the expression of estrogen receptors (ER) α (1) and β (2), progesterone receptor (PR), androgen receptor (AR), as well as PARP-1 via immunohistochemistry and quantitative RT-PCR in 69 tissue samples of desmoid tumors. Immunohistochemistry was quantified using the Immunoreactivity Score (IRS). Overall expression patterns were correlated with clinical-pathologic parameters to determine their value as a prognostic factor. Among the investigated hormone receptors only ERβ showed partial cytoplasmic reactivity. PARP-1 revealed variable nuclear positivity with IRS ranging from 0 to 6. Univariate survival analysis showed that higher expression of estrogen receptor 1 was associated with shorter disease-free survival (p=0.005). Uni- (p=0.03) and multivariate (p=0.003) analyses of mRNA data revealed that higher PARP-1 expression correlated with earlier recurrence. According to this study PARP-1 expression is associated with poorer prognosis, that is faster recurrence, highlighting the possibility of PARP-1-targeting agents as a therapeutic option. Hormone receptors were of minor prognostic relevance in this study.
Beschreibung:Available online 13 December 2019
Gesehen am 23.04.2020
Beschreibung:Online Resource
ISSN:1532-8198
DOI:10.1016/j.anndiagpath.2019.151442

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