Pathology, Department, National Cancer Institute, Cairo University, Egypt.
Exp Mol Pathol. 2012 Aug;93(1):154-61. doi: 10.1016/j.yexmp.2012.04.001. Epub 2012 Apr 6.
Malignant pleural mesothelioma (MPM) is a highly aggressive disease with a generally poor prognosis. Since escape from cell cycle checkpoint control is common in several solid tumors, the present study was performed to evaluate the role of some cell cycle regulatory genes in the development and progression of MPM.
Aberrant expression of p14(ARF), p16(INK4A), p21(waf), p27(KIP), p53, mdm2 and Rb was assessed in 55 MPM cases from Egypt using immunohistochemistry and PCR techniques. Results were correlated with clinico-pathological prognostic factors, overall and disease free survival (OS&DFS).
Altered expression of p14(ARF), p16(INK4A), p21(waf), p27(KIP1), Rb, p53 and mdm2 proteins was detected in 50.9%, 54.5%, 53.3%, 61.8%, 53.3%, 58.2%, and 50.8% of cases, respectively. SV40 infection significantly correlated with p14(ARF), 16(INK4A), p27(kip1) and Rb aberrations (p=0.014, p=0.02, p=0.01, p=-0.01). Asbestos exposure significantly correlated with p53, p21(waf) and mdm2 aberrations (p=0.001, p=0.03, p=0.02). On multivariate analysis PS ≥ 2, p27(KIP1) and Rb aberrations were independent prognostic factors for OS (p=0.016, p=0.011, p=0.003) whereas on tumor recurrence, p27(KIP1) and Rb aberrations were independent prognostic factors for DFS (p=0.002, p=0.03, p=0.01).
MPM is a complex disease characterized by multiple genetic aberrations; some of them involve cell cycle regulatory genes. p14(ARF), p16(INK4A), Rb and p27(KIP1) seem to be involved in SV40-associated MPM whereas mdm2, p53 and p21(WAF) are related to asbestos exposure. In addition to recurrence and PS, only p27(KIP1)and Rb could be used as molecular prognostic markers in MPM.
恶性胸膜间皮瘤（MPM）是一种高度侵袭性疾病，预后通常较差。由于细胞周期检测点控制的逃逸在几种实体瘤中很常见，因此本研究旨在评估一些细胞周期调节基因在 MPM 的发生和发展中的作用。
本研究使用免疫组织化学和 PCR 技术评估了来自埃及的 55 例 MPM 病例中 p14(ARF)、p16(INK4A)、p21(waf)、p27(KIP)、p53、mdm2 和 Rb 的异常表达。结果与临床病理预后因素、总生存期（OS）和无病生存期（DFS）相关。
p14(ARF)、p16(INK4A)、p21(waf)、p27(KIP1)、Rb、p53 和 mdm2 蛋白的异常表达分别在 50.9%、54.5%、53.3%、61.8%、53.3%、58.2%和 50.8%的病例中检测到。SV40 感染与 p14(ARF)、p16(INK4A)、p27(kip1)和 Rb 异常显著相关（p=0.014，p=0.02，p=0.01，p=-0.01）。石棉暴露与 p53、p21(waf)和 mdm2 异常显著相关（p=0.001，p=0.03，p=0.02）。多变量分析显示 PS≥2、p27(KIP1)和 Rb 异常是 OS 的独立预后因素（p=0.016、p=0.011、p=0.003），而在肿瘤复发方面，p27(KIP1)和 Rb 异常是 DFS 的独立预后因素（p=0.002、p=0.03、p=0.01）。
MPM 是一种复杂的疾病，其特征是多种基因异常，其中一些涉及细胞周期调节基因。p14(ARF)、p16(INK4A)、Rb 和 p27(KIP1)似乎与 SV40 相关的 MPM 有关，而 mdm2、p53 和 p21(WAF)与石棉暴露有关。除了复发和 PS 外，只有 p27(KIP1)和 Rb 可以作为 MPM 的分子预后标志物。
