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

Bräutigam, Konstantin; Lindner, Judith; Budczies, Jan; Pahl, Stefan; Kunitz, Annegret; Melcher, Ingo; Wust, Peter; Nebrig, Maxim; Baur, Alexander; Denkert, Carsten; Pfitzner, Berit (2020). PARP-1 expression as a prognostic factor in Desmoid-type fibromatosis. Annals of diagnostic pathology, 44, p. 151442. Elsevier 10.1016/j.anndiagpath.2019.151442

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Bräutigam, Konstantin

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1092-9134

Publisher:

Elsevier

Language:

English

Submitter:

Konstantin Bräutigam

Date Deposited:

11 Aug 2022 17:49

Last Modified:

05 Dec 2022 16:22

Publisher DOI:

10.1016/j.anndiagpath.2019.151442

PubMed ID:

31855806

BORIS DOI:

10.48350/171840

URI:

https://boris.unibe.ch/id/eprint/171840

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