Thoracic Surgery Division, Policlinico Tor Vergata University, Rome, Italy.
Eur J Cardiothorac Surg. 2010 Sep;38(3):245-52. doi: 10.1016/j.ejcts.2010.02.012. Epub 2010 Mar 24.
The expression of cyclooxygenase-2 (COX-2) and cell-cycle proteins (p21 and p27) proves useful in predicting prognosis and orientating therapy in many malignant tumours. Malignant pleural mesothelioma is an uncommon and lethal cancer for which there are limited treatment options. In this study, we evaluated the impact on prognosis and the influence on therapeutic strategy of immunohistochemical expression of COX-2, p21 and p27 in specimens from patients treated for malignant pleural mesothelioma.
We retrospectively reviewed immunohistochemical expression of COX-2, p21 and p27 dichotomised into high and low expression from specimens of 77 consecutive patients undergoing biopsy-plus-pleurodesis (n=6), pleurectomy-decortication (n=44) or extrapleural pneumonectomy (n=27) operations for malignant pleural mesothelioma between 1987 and 2007. Histology was of epithelioid (n=50), biphasic (n=17) and sarcomatoid (n=10) subtypes. Tumour node metastasis (TNM)-stage was I (n=21), II (n=36) and III (n=20). Therapies used were sole adjuvant radiotherapy (n=17), adjuvant radio-chemotherapy (n=56) and neo-adjuvant chemotherapy plus adjuvant radiotherapy (n=4). From 2005 on, preoperative maximal standard uptake value (SUV(MAX)) was also measured by fluorodeoxyglucose positron-emission-tomography. Significance was investigated by Kaplan-Meier survival and Cox regression analysis.
The median survival was 10 months. Survival was negatively influenced by histology (epithelioid vs biphasic vs sarcomatoid) (p=0.009), positive macroscopic resection margins (p=0.016), metastatic mediastinal lymph nodes (p=0.016), high COX-2 (p=0.0001) expression, low p21 (p=0.0001) expression and low p27 (p=0.001) expression. Conversely, neither the type of surgery (biopsy-plus-pleurodesis vs pleurectomy-decortication vs extrapleural pneumonectomy), nor preoperative SUV(MAX) (> or = 6.0 vs <6.0), or combined therapies (sole radiotherapy vs adjuvant radio-chemotherapy vs neo-adjuvant chemotherapy plus adjuvant radiotherapy) reached a significant level of difference. Cox regression analysis showed that only immunohistochemical triple combination of high COX-2 and low p21 and p27 expression influenced survival (p=0.0001, hazard ratio 4.7, 95% confidence intervals 3-11) regardless of type of treatment.
At Cox regression analysis, a combination of high COX-2 and low p21 and p27 expression resulted in the only negative prognosticator of malignant pleural mesothelioma. With this combination, less aggressive surgical options might be preferred.
环氧化酶-2（COX-2）和细胞周期蛋白（p21 和 p27）的表达在许多恶性肿瘤的预后预测和治疗方向上具有重要作用。恶性胸膜间皮瘤是一种罕见且致命的癌症，治疗选择有限。在这项研究中，我们评估了 COX-2、p21 和 p27 的免疫组织化学表达对接受恶性胸膜间皮瘤治疗的患者的预后的影响，并探讨了其对治疗策略的影响。
我们回顾性分析了 77 例连续患者的 COX-2、p21 和 p27 的免疫组织化学表达，这些患者于 1987 年至 2007 年间接受了活检加胸膜固定术（n=6）、胸膜剥脱术（n=44）或胸膜外全肺切除术（n=27）手术治疗。组织学类型为上皮样（n=50）、双相型（n=17）和肉瘤样（n=10）。肿瘤淋巴结转移（TNM）分期为 I 期（n=21）、II 期（n=36）和 III 期（n=20）。使用的治疗方法为单纯辅助放疗（n=17）、辅助放化疗（n=56）和新辅助化疗加辅助放疗（n=4）。自 2005 年以来，还通过氟脱氧葡萄糖正电子发射断层扫描测量了术前最大标准摄取值（SUV(MAX)）。采用 Kaplan-Meier 生存分析和 Cox 回归分析进行显著性检验。
中位生存时间为 10 个月。生存受到组织学（上皮样比双相比肉瘤样）（p=0.009）、阳性大体切除边缘（p=0.016）、转移性纵隔淋巴结（p=0.016）、高 COX-2 表达（p=0.0001）、低 p21 表达（p=0.0001）和低 p27 表达（p=0.001）的负面影响。相反，手术类型（活检加胸膜固定术比胸膜剥脱术比胸膜外全肺切除术）、术前 SUV(MAX)（≥6.0 与<6.0）或联合治疗（单纯放疗与辅助放化疗与新辅助化疗加辅助放疗）均未达到显著差异。Cox 回归分析显示，只有 COX-2 高表达和 p21 和 p27 低表达的三联免疫组化组合才是恶性胸膜间皮瘤的唯一预后不良因素（p=0.0001，危险比 4.7，95%置信区间 3-11），与治疗类型无关。
在 Cox 回归分析中，COX-2 高表达和 p21 和 p27 低表达的组合是恶性胸膜间皮瘤的唯一预后不良因素。有了这种组合，可能会选择不那么激进的手术方案。
