Smith S L, Gugger M, Hoban P, Ratschiller D, Watson S G, Field J K, Betticher D C, Heighway J
Gene Function Group, Roy Castle Lung Cancer Programme (Clinical Dental Sciences), University of Liverpool Cancer Research Centre, 200 London Road, Liverpool L3 9TA, UK.
Br J Cancer. 2004 Oct 18;91(8):1515-24. doi: 10.1038/sj.bjc.6602188.
S100A2 gene products were shown to be frequently and dramatically over-represented in non-small cell lung cancer (NSCLC) lesions over normal tissue by microarray analysis. We have now analysed an independent series of NSCLC tumours and multiple matched normal bronchial epithelial sites by RT-PCR and immunohistochemistry to investigate: whether this expression pattern can be confirmed and whether elevated expression is associated with tumour histology, clinical outcome or preneoplasia. In this second series, S100A2 was strongly expressed in 76% (35 out of 46) of tumours, more frequently in squamous cell than adenocarcinomas (P<0.002). This strong expression was not related to high-level gene amplification, but was associated in one of five informative cases with an allele-specific imbalance in transcript levels. Most tumours strongly expressed the DeltaNp63 transcript, the product of which is a putative regulator of S100A2 transcription and while all but one of the tumours positive for DeltaNp63 expressed S100A2, others negative for this regulator also expressed the gene. Contrary to the hypothesis that S100A2 is a tumour suppressor, no somatic mutations were identified in the coding sequence in 44 tumours. Furthermore, an examination of multiple tumour-free epithelial sites from 20 patients showed that strong expression was often associated with increasing levels of disorder in preinvasive bronchial lesions (P<0.0001).
通过微阵列分析显示，与正常组织相比，S100A2基因产物在非小细胞肺癌（NSCLC）病变中频繁且显著地过度表达。我们现在通过逆转录聚合酶链反应（RT-PCR）和免疫组织化学分析了一系列独立的NSCLC肿瘤以及多个匹配的正常支气管上皮部位，以研究：这种表达模式是否能够得到证实，以及表达升高是否与肿瘤组织学、临床结果或肿瘤形成前状态相关。在这第二个系列研究中，76%（46例中的35例）的肿瘤中S100A2强烈表达，在鳞状细胞癌中比腺癌中更频繁（P<0.002）。这种强烈表达与高水平基因扩增无关，但在五个信息充分的病例中有一例与转录水平的等位基因特异性失衡有关。大多数肿瘤强烈表达DeltaNp63转录本，其产物是S100A2转录的假定调节因子，虽然DeltaNp63阳性的肿瘤中除一例之外均表达S100A2，但该调节因子阴性的其他肿瘤也表达该基因。与S100A2是肿瘤抑制因子的假设相反，在44个肿瘤的编码序列中未发现体细胞突变。此外，对20例患者的多个无肿瘤上皮部位进行检查发现，强烈表达通常与侵袭前支气管病变中紊乱程度的增加相关（P<0.0001）。
