Mishra Shashi Prakash, Kar Amrita Ghosh, Karthik J S, Srivastava Aviral, Khanna Rahul, Meena Ram Niwas
Department of General Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP, India.
Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP, India.
J Midlife Health. 2022 Jul-Sep;13(3):213-224. doi: 10.4103/jmh.jmh_132_22. Epub 2023 Jan 14.
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.
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.
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 ( < 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) ( = 0.002), postmenopausal women ( = 0.029), higher TNM stage (Stage II and III) ( = 0.014), higher histological grade (grade 2) ( = 0.043), and presence of lymphovascular invasion ( = 0.015). Enhanced PARP1 expression is closely correlated with positive estrogen receptor status ( = 0.001) and PR status ( = 0.001). Overall PARP and nPARP overexpression was significantly associated with ER- ( = 0.006 and = 0.008) and PR-positive ( = 0.006 and = 0.008) patients. The PARP and nPARP overexpression was significantly associated with nontriple-negative BC patients ( = 0.001 and = 0.001).
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.
聚(腺苷二磷酸 - 核糖)聚合酶(PARP)抑制剂用于乳腺癌(BC)治疗一直存在争议,因此迫切需要了解PARP1蛋白的表达情况及其预后作用。在本研究中,我们比较了BC患者和良性乳腺疾病(BBD)患者中PARP的表达情况,并分析了PARP表达与BC临床病理参数之间的关联。
本研究纳入了2019年至2021年间30例新诊断的可手术BC患者,这些患者计划接受手术且未进行新辅助化疗,同时纳入15例BBD患者作为对照。对组织样本进行前瞻性免疫组织化学分析。抗人PARP1兔多克隆抗体在细胞核中呈强阳性。内部对照为脂肪组织,BBD作为外部对照。使用乘法快速评分法评估PARP1表达。
BC患者的平均年龄为51.30±10.694岁(范围:25 - 75岁),而BBD患者年龄低于30岁。与BBD相比,BC患者中25例(83.3%)PARP过表达,5例(16.7%)弱表达;BBD患者中仅2例(13.3%)PARP过表达,13例(86.6%)弱表达,差异具有统计学意义(<0.001)。在BC患者中,22例(73.3%)细胞核PARP(nPARP)过表达,8例(26.7%)nPARP弱表达,5例(16.7%)细胞质过表达。将PARP表达与临床病理参数进行比较,PARP过表达与老年人群(年龄>50岁)(=0.002)、绝经后女性(=0.029)、较高的TNM分期(II期和III期)(=0.014)、较高的组织学分级(2级)(=0.043)以及存在淋巴管浸润(=0.015)显著相关。PARP1表达增强与雌激素受体阳性状态(=0.001)和孕激素受体状态(=0.001)密切相关。总体而言,PARP和nPARP过表达与雌激素受体阴性(=0.006和=0.008)以及孕激素受体阳性(=0.006和=0.008)患者显著相关。PARP和nPARP过表达与非三阴性BC患者显著相关(=0.001和=0.001)。
我们在文献中未发现任何比较BC患者和BBD患者中PARP表达的研究。基于我们观察的结果,我们得出结论,PARP过表达是BC患者预后不良的标志物。