Claudin-1 Protein Expression Is a Good Prognostic Factor in Non-Small Cell Lung Cancer, but only in Squamous Cell Carcinoma Cases
Claudin-1 Protein Expression Is a Good Prognostic Factor in Non-Small Cell Lung Cancer, but only in Squamous Cell Carcinoma Cases
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DOI：
10.1007/s12253-016-0115-0
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发表时间：
2017-01-01
影响因子：
2.8
通讯作者：
Schaff, Zsuzsa
中科院分区：
文献类型：
--
作者：
Moldvay, Judit;Fabian, Katalin;Schaff, Zsuzsa
本研究旨在探讨非小细胞肺癌组织学亚型中claudin（CLDN）蛋白表达与临床病理参数及生存期的相关性。对137例病理I期原发性支气管癌的存档手术切除标本进行了检查，其中包括49例非鳞片状腺癌（ADC），46例鳞片状腺癌（L-ADC）和42例鳞状细胞癌（SCC）。使用针对CLDN 1、CLDN 2、CLDN 3、CLDN 4、CLDN 7蛋白的抗体进行免疫组织化学（IHC）以及半定量估计（IHC评分0-5）。L-ADC的Claudin IHC评分与ADC（分别为CLDN 1：p = 0.009、CLDN 2：p = 0.005、CLDN 3：p = 0.004、CLDN 4：p = 0.001、CLDN 7：p < 0.001）和SCC（分别为CLDN 1：p <0.001、CLDN 3：p < 0.001、CLDN 7：p < 0.001）显著不同。在ADC和L-ADC中可以证明高度显著的CLDN 3-CLDN 4平行表达（在两者中p < 0.001），这在SCC中没有观察到（p = 0.131）。ADC和SCC显示与吸烟无关，而在L-ADC的情况下，较重的吸烟与较高的CLDN 3表达相关（p = 0.020）。关于紧密连接蛋白表达和存活，在SCC中，CLDN 1 IHC阳性和更好的存活之间可以证明显著相关性（p = 0.038）。在NSCLC整体中，当与CLDN 2 IHC评分为0-1对2-5的病例相比时，高CLDN 2表达被证明是更好的预后因素（p = 0.009），然而，当单独分析时，没有一个组织学亚组显示CLDN 2表达与总生存期之间的相关性。紧密连接蛋白表达模式不仅在SCC-ADC和SCC-L-ADC之间显著不同，而且在L-ADC和ADC组织学亚组之间也显著不同，这强烈强调了L-ADC代表ADC组内的不同实体。CLDN 1过表达是NSCLC的良好预后因素，但仅在SCC亚组中。
The aim of the study was to investigate the correlation between claudin (CLDN) protein expression and clinicopathological parameters as well as survival in histological subtypes of non-small cell lung cancer. Archived surgical resection specimens of 137 pathologic stage I primary bronchial cancers including 49 adenocarcinomas of non-lepidic variants (ADC), 46 adenocarcinomas of lepidic variants (L-ADC), and 42 squamous cell carcinomas (SCC) were examined. Immunohistochemistry (IHC) using antibodies against CLDN1,-2,-3,-4,-7 proteins as well as semiquantitative estimation (IHC scores 0-5) were performed. Claudin IHC scores of L-ADC differed significantly from ADC (CLDN1: p = 0.009, CLDN2: p = 0.005, CLDN3: p = 0.004, CLDN4: p = 0.001, CLDN7: p < 0.001, respectively) and SCC (CLDN1: p < 0.001, CLDN3: p < 0.001, CLDN7: p < 0.001, respectively). Highly significant CLDN3-CLDN4 parallel expression could be demonstrated in ADC and L-ADC (p < 0.001 in both), which was not observed in SCC (p = 0.131). ADC and SCC showed no correlation with smoking, whereas in case of L-ADC heavier smoking correlated with higher CLDN3 expression (p = 0.020). Regarding claudin expression and survival, in SCC significant correlation could be demonstrated between CLDN1 IHC positivity and better survival (p = 0.038). In NSCLC as a whole, high CLDN2 expression proved to be a better prognostic factor when compared with cases where CLDN2 IHC score was 0-1 vs. 2-5 (p = 0.009), however, when analyzed separately, none of the histological subgroups showed correlation between CLDN2 expression and overall survival. The claudin expression pattern was significantly different not only between the SCC-ADC and SCC-L-ADC but also between the L-ADC and ADC histological subgroups, which strongly underlines that L-ADC represents a distinct entity within the ADC group. CLDN1 overexpression is a good prognostic factor in NSCLC, but only in the SCC subgroup.