Hemida Aiat Shaban, Abdelaziz Reham Ahmed, Abd El-Wahed Moshira Mohammed, Asaad Nancy Yousef, Serag El-Dien Marwa Mohammed, Elshahat Ali Hend Ali
Department of Pathology, Faculty of Medicine, Menoufia University, Shebin El Kom, Egypt.
Department of Clinical Oncology& Nuclear Medicine, Faculty of Medicine, Menoufia University, Shebin El Kom, Egypt.
Iran J Pathol. 2024 Spring;19(2):177-192. doi: 10.30699/IJP.2024.2014367.3198. Epub 2023 Feb 15.
BACKGROUND & OBJECTIVE: The regulator of chromosome condensation 2 (RCC2) and RAS-related C3 botulinum toxin substrate 1 (Rac1) have been implicated in the promotion of breast cancer cell proliferation and migration. The signaling pathway involving p53/RCC2/Rac1 has been proposed to contribute to the regulation of colon cancer metastasis. However, until now, this pathway has not been thoroughly investigated in breast cancer. This study seeks to explore the influence of immunohistochemical expression and the correlation among RCC2, Rac1, and p53 in breast infiltrating ductal carcinoma (IDC).
Immunostaining was performed on 120 breast IDC specimens using RCC2, Rac1, and p53 antibodies. Statistical analyses were conducted to examine the correlations between these antibodies.
A Positive expression of RCC2, Rac1, and p53 was observed in 116 (96.7%), 120 (100%), and 33 (27.5%) of the breast cancer cases, respectively. RCC2, Rac1, and p53 demonstrated association with poor prognostic parameters such as frequent mitoses, high Ki-67 status, positive lymphovascular invasion (LVI), and advanced tumor stage. A highly significant direct correlation was found between each immunohistochemical marker and the other two markers. Shorter overall survival was linked to multifocal tumors (=0.017), advanced tumor stage (T3) (=0.010), Luminal B subtype (=0.015), progressive disease (=0.003), positive Her2neu status (=0.008), and metastasis to distant organs (<0.001). However, RCC2, Rac1, and p53 did not exhibit a significant association with overall survival.
The high expression levels of RCC2, Rac1, and p53 in breast IDC suggest their potential role in tumor behavior. The association of RCC2 and Rac1 with poor prognostic parameters may serve as predictive indicators for aggressive tumors, thus implying that targeted therapy could be beneficial in the treatment of breast cancer.
染色体凝聚调节因子2(RCC2)和RAS相关的C3肉毒杆菌毒素底物1(Rac1)被认为与乳腺癌细胞的增殖和迁移促进有关。有人提出涉及p53/RCC2/Rac1的信号通路有助于调节结肠癌转移。然而,迄今为止,该通路在乳腺癌中尚未得到充分研究。本研究旨在探讨免疫组化表达以及RCC2、Rac1和p53在乳腺浸润性导管癌(IDC)中的相关性。
使用RCC2、Rac1和p53抗体对120例乳腺IDC标本进行免疫染色。进行统计分析以检验这些抗体之间的相关性。
在116例(96.7%)、120例(100%)和33例(27.5%)乳腺癌病例中分别观察到RCC2、Rac1和p53的阳性表达。RCC2、Rac1和p53与不良预后参数相关,如频繁有丝分裂、高Ki-67状态、阳性淋巴管浸润(LVI)和晚期肿瘤分期。在每个免疫组化标记物与其他两个标记物之间发现高度显著的直接相关性。较短的总生存期与多灶性肿瘤(=0.017)、晚期肿瘤分期(T3)(=0.010)、Luminal B亚型(=0.015)、疾病进展(=0.003)、阳性Her2neu状态(=0.008)以及远处器官转移(<0.001)有关。然而,RCC2、Rac1和p53与总生存期无显著关联。
乳腺IDC中RCC2、Rac1和p53的高表达水平提示它们在肿瘤行为中的潜在作用。RCC2和Rac1与不良预后参数的关联可能作为侵袭性肿瘤的预测指标,因此意味着靶向治疗可能对乳腺癌治疗有益。