Department of Thoracic Surgery, Athens Naval Hospital, Athens.
Onco Targets Ther. 2012;5:363-73. doi: 10.2147/OTT.S36474. Epub 2012 Nov 21.
S100 proteins are involved in carcinogenesis, metastasis, and survival. S100A2 is a member of the S100 family, and its expression and precise role in patients with non-small cell lung carcinoma (NSCLC) has been debated. Therefore, we examined the immunohistochemical expression patterns of S100A2 in NSCLC in relation to clinicopathological parameters, important molecular biomarkers, and patient outcome. Microarray data for 74 paraffin-embedded specimens from patients with NSCLC were immunostained for S100A2 and p53 proteins. Immunohistochemical staining patterns of S100A2 in the NSCLC tissue samples examined were either nuclear (nS100A2), cytoplasmic (cS100A2), or both. A significant association between nS100A2 positivity and better disease-free interval was observed (hazards ratio 0.47; 95% confidence interval 0.23-0.99; P = 0.047). Similarly, cS100A2 negativity was marginally associated with shorter overall survival (P = 0.07). Patients without lymphatic infiltration and an earlier disease stage had significantly better overall survival and disease-free interval. The S100A2 expression pattern in operable NSCLC varies widely, and this differential expression (nuclear, cytoplasmic or both) seems to correlate with prognosis. Intensity of expression was highest in the early and advanced stages, and equally distributed in the middle stages. This observation may be indicative of a dual role for this protein both during earlier and advanced disease stages, and may also explain the differential immunoexpression of S100A2. Analysis of the disease-free interval showed that nS100A2-negative and p53-positive expression was associated with a statistically significant (P = 0.003) shorter disease-free interval in comparison with nS100A2-positive and p53-negative expression (12 versus 30 months, respectively). Further studies are required to establish whether S100A2 protein may have a substantial role as a prognostic or predictive indicator in this unfavorable group of patients.
S100 蛋白参与致癌、转移和存活。S100A2 是 S100 家族的成员，其在非小细胞肺癌 (NSCLC) 患者中的表达和确切作用一直存在争议。因此，我们研究了 S100A2 在 NSCLC 中的免疫组织化学表达模式与临床病理参数、重要的分子生物标志物和患者预后的关系。对 74 例 NSCLC 患者的石蜡包埋标本的微阵列数据进行了 S100A2 和 p53 蛋白的免疫染色。检查的 NSCLC 组织样本中 S100A2 的免疫染色模式为核 (nS100A2)、细胞质 (cS100A2) 或两者兼有。nS100A2 阳性与无病间隔时间延长显著相关 (风险比 0.47；95%置信区间 0.23-0.99；P=0.047)。同样，cS100A2 阴性与总生存期较短有一定关联 (P=0.07)。无淋巴浸润和早期疾病阶段的患者总生存期和无病间隔显著延长。可手术 NSCLC 中的 S100A2 表达模式差异很大，这种差异表达 (核、细胞质或两者兼有) 似乎与预后相关。在早期和晚期阶段，表达强度最高，在中期阶段均匀分布。这一观察结果可能表明该蛋白在疾病早期和晚期都具有双重作用，也可能解释 S100A2 的免疫表达差异。无病间隔分析表明，与 nS100A2 阳性和 p53 阴性表达相比，nS100A2 阴性和 p53 阳性表达与无病间隔显著缩短相关 (分别为 12 个月和 30 个月，P=0.003)。需要进一步研究以确定 S100A2 蛋白是否可以作为这组不利患者的预后或预测指标发挥重要作用。
