非小细胞肺癌中Bcl-2和COX-2表达的预后意义

Prognostic value of Bcl-2 and cyclooxygenase-2 expressions in non-small cell lung cancer:a tissue microarray analysis of 88 cases

目的探讨Bcl-2和COX-2表达与非小细胞肺癌(non-smallcelllungcanc-er,NSCLC)预后的关系。方法将88例NSCLC及10例正常肺组织标本制作成组织芯片,应用免疫组织化学SP法检测Bcl-2和COX-2的表达,并与临床病理特征及长期生存进行比较分析。结果Bcl-2胞质和胞核阳性表达率分别为54.5%和42.0%,COX-2胞质阳性表达率为71.6%,而正常肺组织均为阴性,NSCLC患者的Bcl-2胞质和胞核表达和COX-2表达明显高于正常肺组织,P值分别为0.001、0.012和0.000。Bcl-2胞质表达在男性、吸烟者、鳞癌、无淋巴结转移者中表达升高,P值分别为0.001、0.000、0.000和0.002,而与年龄、分化程度和肿瘤大小无关。Bcl-2胞核表达在女性、不吸烟者、腺癌和肿瘤大小为T3和T4者中表达升高,P值分别为0.001、0.006、0.000和0.025,而与年龄、分化程度和淋巴结是否转移无关。COX-2在女性、不吸烟者、腺癌和淋巴结转移阳性者中表达升高,P值分别为0.005、0.027、0.001和0.003,与年龄、分化程度和肿瘤大小无关。Bcl-2胞质表达的患者生存时间更长,而Bcl-2胞核表达的患者生存时间更短。COX-2表达者生存时间短。多因素分析显示,Bcl-2和COX-2不是影响NSCLC预后的独立危险因素。结论NSCLC患者中Bcl-2胞质和胞核表达可能具有相反的预后意义,Bcl-2胞质表达者预后好,而Bcl-2胞核表达者预后差,COX-2阳性表达者预后差,两者联合检测可能在NSCLC预后判定中有重要作用。

OBJECTIVE： To investigate the prognostic value of Bcl-2 and cyclooxygenase-2 （COX-2） in patients with non-small cell lung cancer （NSCLC）. METHODS： Expressions of Bcl-2 and COX-2 were assayed accessed by immunohistochemical staining on tissue microarray sections made of 88 cases of NSCLC and 10 cases of normal lung samples, and the results were compared with relevant clinical and pathologic data, All cases were followed up for more than 5 years. RESULTS： Cytoplasmic and nuclear expressions of Bcl-2 in NSCLC were detected in 54.5% and 42.0%, respectively. Cytoplasmic expression of COX-2 was detected in 71.6%, Neither Bcl-2 nor COX-2 expression was observed in normal lung tissues. Expressions of cytoplasmic and nuclear Bcl-2 and COX-2 in NSCLC were signifieantly higher than those in normal lung tissues （P= 0. 001, 0. 012 and 0. 000, respectively）. Cytoplasmic Bcl-2 expression was significantly higher in groups with male, smokers, squamous cell carcinoma and no lymph node involvement （P = 0. 001, 0. 000, 0. 000 and 0. 002, respectively）, and nuclear Bcl-2 expression was significantly higher in groups with male, non-smokers, adenocarcinoma and tumor size with T3 and T4 （P = 0. 001, 0. 006, 0, 000 and 0. 025, respectively）. The positive expressions of COX-2 was significantly higher in groups with female, nonsmokers, adenocarcinoma and lymph node metastasis （P= 0. 005, 0. 027, 0. 001 and 0. 003. respectively）. The patients with positives expression of nuclear Bcl-2 and COX-2 had worse overall survival, whereas the patients with positive expression of cytoplasmic Bcl-2 had better overall survival. Multivariate analysis using Cox regression modal showed that neither Bcl-2 nor COX-2 was the important independent prognostic factor for survival. CONCLUSIONS： Cytoplasmic and nuclear expression of Bcl-2 might possess completely opposite prognostic significance in patients with NSCLC, and aberrant expression of COX-2 is related to shorter overall survival, which suggests both Bcl-2 and COX-2 may be useful as indicators for prognosis in NSCLC.