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Expression of Poly(Adenosine Diphosphate-Ribose) Polymerase Protein in Breast Cancer

BACKGROUND: The use of poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors for breast cancer (BC) therapy is the subject of debate, and there is an urgent need to understand much the expression and prognostic role of the PARP1 protein. In this study, we have compared the expression of PA...

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Autores principales: Akanksha, Mishra, Shashi Prakash, Kar, Amrita Ghosh, Karthik, J. S., Srivastava, Aviral, Khanna, Rahul, Meena, Ram Niwas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer - Medknow 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10025820/
https://www.ncbi.nlm.nih.gov/pubmed/36950213
http://dx.doi.org/10.4103/jmh.jmh_132_22
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author Akanksha,
Mishra, Shashi Prakash
Kar, Amrita Ghosh
Karthik, J. S.
Srivastava, Aviral
Khanna, Rahul
Meena, Ram Niwas
author_facet Akanksha,
Mishra, Shashi Prakash
Kar, Amrita Ghosh
Karthik, J. S.
Srivastava, Aviral
Khanna, Rahul
Meena, Ram Niwas
author_sort Akanksha,
collection PubMed
description BACKGROUND: The use of poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors for breast cancer (BC) therapy is the subject of debate, and there is an urgent need to understand much the expression and prognostic role of the PARP1 protein. In this study, we have compared the expression of PARP between BC and benign breast disease (BBD) patients and also analyzed the association of PARP expression with clinicopathological parameters in BC. METHODS: The study consists of 30 patients with newly diagnosed operable BC who were planned for surgery without neoadjuvant chemotherapy and 15 patients of BBD as a control between 2019 and 2021. Immunohistochemical analyses were performed prospectively on tissue samples. Anti-human PARP1 rabbit polyclonal antibody gives strong nuclear positivity. Internal control was the adipose tissue and the BBD acted as the external control. PARP1 expression was evaluated using the multiplicative quickscore method. RESULTS: The mean age for BC patients was 51.30 ± 10.694 years (range: 25–75 years) while BBD was below 30 years. Overexpression of PARP was present in 25 (83.3%) and weak expression in 5 (16.7%) of BC patients compared to BBD, only 2 (13.3%) patients demonstrated an overexpression of PARP, and 13 (86.6%) patients showed weak expression which showed significant association (P < 0.001). In BC, nuclear PARP (nPARP) overexpression was seen in 22 (73.3%) patients and weak expression of nPARP in 8 (26.7%), whereas 5 (16.7%) patients showed cytoplasmic overexpression. On comparing expression of PARP with clinicopathological parameters, PARP overexpression was significantly associated with older population (age >50 years) (P = 0.002), postmenopausal women (P = 0.029), higher TNM stage (Stage II and III) (P = 0.014), higher histological grade (grade 2) (P = 0.043), and presence of lymphovascular invasion (P = 0.015). Enhanced PARP1 expression is closely correlated with positive estrogen receptor status (P = 0.001) and PR status (P = 0.001). Overall PARP and nPARP overexpression was significantly associated with ER- (P = 0.006 and P = 0.008) and PR-positive (P = 0.006 and P = 0.008) patients. The PARP and nPARP overexpression was significantly associated with nontriple-negative BC patients (P = 0.001 and P = 0.001). CONCLUSION: We have not come across any study in the literature to compare PARP expression in BC and BBD patients. On the basis of our observations, we concluded that PARP overexpression is a poor prognostic marker in BC.
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spelling pubmed-100258202023-03-21 Expression of Poly(Adenosine Diphosphate-Ribose) Polymerase Protein in Breast Cancer Akanksha, Mishra, Shashi Prakash Kar, Amrita Ghosh Karthik, J. S. Srivastava, Aviral Khanna, Rahul Meena, Ram Niwas J Midlife Health Original Article BACKGROUND: The use of poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors for breast cancer (BC) therapy is the subject of debate, and there is an urgent need to understand much the expression and prognostic role of the PARP1 protein. In this study, we have compared the expression of PARP between BC and benign breast disease (BBD) patients and also analyzed the association of PARP expression with clinicopathological parameters in BC. METHODS: The study consists of 30 patients with newly diagnosed operable BC who were planned for surgery without neoadjuvant chemotherapy and 15 patients of BBD as a control between 2019 and 2021. Immunohistochemical analyses were performed prospectively on tissue samples. Anti-human PARP1 rabbit polyclonal antibody gives strong nuclear positivity. Internal control was the adipose tissue and the BBD acted as the external control. PARP1 expression was evaluated using the multiplicative quickscore method. RESULTS: The mean age for BC patients was 51.30 ± 10.694 years (range: 25–75 years) while BBD was below 30 years. Overexpression of PARP was present in 25 (83.3%) and weak expression in 5 (16.7%) of BC patients compared to BBD, only 2 (13.3%) patients demonstrated an overexpression of PARP, and 13 (86.6%) patients showed weak expression which showed significant association (P < 0.001). In BC, nuclear PARP (nPARP) overexpression was seen in 22 (73.3%) patients and weak expression of nPARP in 8 (26.7%), whereas 5 (16.7%) patients showed cytoplasmic overexpression. On comparing expression of PARP with clinicopathological parameters, PARP overexpression was significantly associated with older population (age >50 years) (P = 0.002), postmenopausal women (P = 0.029), higher TNM stage (Stage II and III) (P = 0.014), higher histological grade (grade 2) (P = 0.043), and presence of lymphovascular invasion (P = 0.015). Enhanced PARP1 expression is closely correlated with positive estrogen receptor status (P = 0.001) and PR status (P = 0.001). Overall PARP and nPARP overexpression was significantly associated with ER- (P = 0.006 and P = 0.008) and PR-positive (P = 0.006 and P = 0.008) patients. The PARP and nPARP overexpression was significantly associated with nontriple-negative BC patients (P = 0.001 and P = 0.001). CONCLUSION: We have not come across any study in the literature to compare PARP expression in BC and BBD patients. On the basis of our observations, we concluded that PARP overexpression is a poor prognostic marker in BC. Wolters Kluwer - Medknow 2022 2023-01-14 /pmc/articles/PMC10025820/ /pubmed/36950213 http://dx.doi.org/10.4103/jmh.jmh_132_22 Text en Copyright: © 2023 Journal of Mid-life Health https://creativecommons.org/licenses/by-nc-sa/4.0/This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
spellingShingle Original Article
Akanksha,
Mishra, Shashi Prakash
Kar, Amrita Ghosh
Karthik, J. S.
Srivastava, Aviral
Khanna, Rahul
Meena, Ram Niwas
Expression of Poly(Adenosine Diphosphate-Ribose) Polymerase Protein in Breast Cancer
title Expression of Poly(Adenosine Diphosphate-Ribose) Polymerase Protein in Breast Cancer
title_full Expression of Poly(Adenosine Diphosphate-Ribose) Polymerase Protein in Breast Cancer
title_fullStr Expression of Poly(Adenosine Diphosphate-Ribose) Polymerase Protein in Breast Cancer
title_full_unstemmed Expression of Poly(Adenosine Diphosphate-Ribose) Polymerase Protein in Breast Cancer
title_short Expression of Poly(Adenosine Diphosphate-Ribose) Polymerase Protein in Breast Cancer
title_sort expression of poly(adenosine diphosphate-ribose) polymerase protein in breast cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10025820/
https://www.ncbi.nlm.nih.gov/pubmed/36950213
http://dx.doi.org/10.4103/jmh.jmh_132_22
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