Bahnasy Abeer A, El-Din Raghda Shehab, Sabri Nagwa Ali, Abdel-Rahman Chahd A, Bastawisy Ahmed El
Tissue Culture and Cytogenetics Unit, Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
Clinical Pharmacy Department, Ain Shams University, Cairo, Egypt.
Cancer Genet. 2018 Dec;228-229:83-92. doi: 10.1016/j.cancergen.2018.10.001. Epub 2018 Oct 8.
Malignant Pleural Mesothelioma (MPM) is a lethal cancer with few therapeutic options. Patients with MPM have a poor prognosis, with estimated 1 year median survival and currently no treatment is curative. The BRCA associated protein 1 (BAP1) has the highest prevalence of protein-altering mutations identified in MPM.
Assessment of the frequency and pattern of BAP1 gene mutations in Egyptian patients with advanced sporadic MPM in relation to disease progression and survival rates in order to identify a novel therapeutic target for MPM.
This prospective, cohort study included 122 patients who were diagnosed and treated as advanced MPM. BAP1 gene mutations were assessed from circulating tumor cells (CTCs) by polymerase chain reaction (PCR) and sequencing and these mutations have been confirmed using the tumor tissue. BAP1 immunohistochemistry was performed using the Dako Envision visualization system. The relationship between BAP1 gene mutations, PFS and OS rates was assessed using the log rank test. The relationship between BAP1 gene mutations, clinical response and patient's clinicopathological characteristics was assessed using chi-square test.
Forty seven (38.5%) MPM cases showed one or more mutations in BAP1 gene. The presence of BAP1 mutations associated significantly with BAP1 protein expression (p < 0.001), the incidence of organ metastasis (p = 0.04), PFS after second line treatment (p = 0.04) and clinical response after second line treatment (p = 0.01) only.
BAP1 gene mutations are relatively common in Egyptian patients with advanced sporadic MPM. BAP1 mutations are associated with disease progression especially after second line therapy and the incidence of organ metastasis.
恶性胸膜间皮瘤（MPM）是一种致命癌症，治疗选择有限。MPM患者预后较差，估计中位生存期为1年，目前尚无治愈性治疗方法。在MPM中，与乳腺癌相关蛋白1（BAP1）发生蛋白改变突变的发生率最高。
评估埃及晚期散发性MPM患者中BAP1基因突变的频率和模式与疾病进展及生存率的关系，以确定MPM的新治疗靶点。
这项前瞻性队列研究纳入了122例被诊断为晚期MPM并接受治疗的患者。通过聚合酶链反应（PCR）和测序从循环肿瘤细胞（CTC）中评估BAP1基因突变，并使用肿瘤组织进行了确认。使用Dako Envision可视化系统进行BAP1免疫组织化学检测。使用对数秩检验评估BAP1基因突变、无进展生存期（PFS）和总生存期（OS）率之间的关系。使用卡方检验评估BAP1基因突变、临床反应与患者临床病理特征之间的关系。
47例（38.5%）MPM病例显示BAP1基因存在一个或多个突变。BAP1突变的存在仅与BAP1蛋白表达（p < 0.001）、器官转移发生率（p = 0.04）、二线治疗后的PFS（p = 0.04）和二线治疗后的临床反应（p = 0.01）显著相关。
BAP1基因突变在埃及晚期散发性MPM患者中相对常见。BAP1突变与疾病进展相关，尤其是二线治疗后以及器官转移发生率。
