Basic Research Laboratory, Shanghai Chest Hospital affiliated to Shanghai Jiao Tong University, Shanghai 200030, China.
Chin Med J (Engl). 2012 Aug;125(16):2811-8.
The prognostic relevance of World Health Organization (WHO) subtypes within type B thymomas is still controversial. Understanding of the molecular characteristics of the different histologic types of thymomas will provide meaningful information for diagnosis and therapeutic management in type B thymoma.
Proteins extracted from twelve type B thymoma tissue specimens (six type B1 and six type B2) were analyzed by two-dimensional electrophoresis (2-DE) coupled with MALDI-TOF-MS. Differentially expressed proteins were then assayed in sixty-nine type B thymoma tissues (including B1, B2 and B3) by tissue array analysis with immunohistochemistry staining. The relationship of their expression with clinicopathological parameters, such as tumor stage or WHO classification, was estimated by Spearman's Rank Correlation Test.
Sixteen differentially expressed proteins between type B1 and B2 thymoma tissues were identified. The differential levels of ezrin and glutathione S-transferase pi (GSTP1) were validated using immunohistochemistry staining. A statistically significant difference was observed in the positive rate of ezrin expression between type B1 thymoma and type B3 thymoma (Z = -2.963, P < 0.01). Ezrin showed a tendency to be expressed in higher classification tumors from type B1 to B3. A statistical analysis demonstrated that type B2 and B3 tumors had significantly higher positive expression of GSTP1 than the B1 group (type B2 vs. B1: Z = -2.582, P = 0.01; type B3 vs. B1: Z = -4.012, P ≤ 0.001). The results also showed a strong correlation between GSTP1 and WHO type staging of B1 to B3 tumors (Spearman's correlation coefficient: 0.633, P ≤ 0.001). Statistical analysis showed that there was close correlation between GSTP1 and ezrin expression with the clinical stage (Spearman's correlation coefficients, ezrin: 0.481, P < 0.05; GSTP1: 0.484, P < 0.01).
Differentially expressed proteins between type B1 and B2 thymoma tissues were analyzed by comparative proteomic analysis. The techniques of proteomic analysis and tissue array provide a potential tool for screening of key molecules in type B thymoma histological sub-classifications. The statistical analysis of ezrin and GSTP1 expression by immunohistochemistry, especially GSTP1, may be a useful approach for type B thymoma classification.
世界卫生组织（WHO）B 型胸腺瘤亚型的预后相关性仍存在争议。了解不同组织学类型胸腺瘤的分子特征将为 B 型胸腺瘤的诊断和治疗管理提供有意义的信息。
通过二维电泳（2-DE）结合 MALDI-TOF-MS 分析 12 例 B 型胸腺瘤组织标本（6 例 B1 和 6 例 B2）中的蛋白质。然后，通过免疫组织化学染色的组织阵列分析检测 69 例 B 型胸腺瘤组织（包括 B1、B2 和 B3）中差异表达的蛋白质。通过 Spearman 秩相关检验评估它们的表达与肿瘤分期或 WHO 分类等临床病理参数的关系。
鉴定出 B1 和 B2 胸腺瘤组织之间 16 种差异表达的蛋白质。使用免疫组织化学染色验证了 ezrin 和谷胱甘肽 S-转移酶 pi（GSTP1）的差异水平。B1 胸腺瘤和 B3 胸腺瘤之间 ezrin 表达的阳性率存在统计学差异（Z=-2.963，P<0.01）。ezrin 在从 B1 到 B3 的分类较高的肿瘤中表达趋势较高。统计分析表明，B2 和 B3 肿瘤的 GSTP1 阳性表达明显高于 B1 组（B2 与 B1：Z=-2.582，P=0.01；B3 与 B1：Z=-4.012，P≤0.001）。结果还表明，GSTP1 与 B1 至 B3 肿瘤的 WHO 分期之间存在很强的相关性（Spearman 相关系数：0.633，P≤0.001）。统计分析表明，GSTP1 与 ezrin 表达与临床分期密切相关（Spearman 相关系数，ezrin：0.481，P<0.05；GSTP1：0.484，P<0.01）。
通过比较蛋白质组学分析分析了 B1 和 B2 胸腺瘤组织之间差异表达的蛋白质。蛋白质组分析和组织阵列技术为筛选 B 型胸腺瘤组织学亚分类中的关键分子提供了潜在工具。免疫组织化学分析 ezrin 和 GSTP1 表达的统计分析，特别是 GSTP1，可能是 B 型胸腺瘤分类的有用方法。
