S100A2 is strongly expressed in airway basal cells, preneoplastic bronchial lesions and primary non-small cell lung carcinomas

Abstract

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 (Po0.002). 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 DNp63 transcript, the product of which is a putative regulator of S100A2 transcription and while all but one of the tumours positive for DNp63 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 (Po0.0001).

S100A2 (S100 calcium binding protein A2)

“…High expression of S100A2 is associated with metastasis and predicts survival in early stages of NSCLC. These findings are supported by studies in a mouse model of non-small cell lung cancer (NSCLC) where NOD/SCID mice xenografted with NSCLC cells overexpressing S100A2 demonstrated significantly more metastases than vector alone transfected cells (Heighway et al, 2002;Diederichs et al, 2004;Smith et al, 2004;Wang et al, 2005;Zech et al, 2006;Bartling et al, 2007;Bulk et al, 2009;Strazisar et al, 2009a;Strazisar et al, 2009b).…”

Diagnostic utility of S100A1 expression in renal cell neoplasms: an immunohistochemical and quantitative RT-PCR study

“…27 Recent investigations have emphasized the potential diagnostic and oncogenetic role of S100 proteins in a variety of tumors. [28][29][30][31][32][33][34] In this study, we found that S100A1 protein is expressed in renal oncocytomas, and in clear cell and papillary renal cell carcinomas but not in chromophobe renal cell carcinomas. We found significant statistical differences between S100A1 immunoexpression in clear cell and chromophobe renal cell carcinomas (Po0.001), which suggests that S100A1 could be a useful tool in their differential diagnosis.…”

The expression of COX-2, hTERT, MDM2, LATS2 and S100A2 in different types of non-small cell lung cancer (NSCLC)

“…The S100A2 gene is significantly differently expressed in ADC versus SCC, an observation that had already been detected with IHC and RT-PCR in 2004 by Smith et al [38]. Many discrepancies in the results concerning S100A2 expression have arisen: it was stated that the gene is down-regulated in NSCLC, while further research showed that its expression levels depend on the stage of the NSCLC, and that in the main, S100A2 is over-expressed in lung cancer tumours.…”

“…In the most recent studies, it was proposed that over-expression of the S100A2 gene in stage I NSCLC indicates a poor prognosis, and may be used to identify patients with early-stage NSCLC [39], or even as a predictor of distant metastasis [40]. There could also be differences in the levels of expression according to the NSCLC type [38]. We present here data on the COX-2, hTERT, MDM2, LATS2 and S100A2 expression levels in NSCLC, and how they relate to the NSCLC type.…”

“…The results of expression analysis of the S100A2 gene in NSCLC are somewhat contradictory. Early studies suggested that S100A2 expression is suppressed at an early stage of lung carcinogenesis [37], but later data indicated that it might be strongly expressed in the majority of NSCLC tumours [37,38]. In the most recent studies, it was proposed that over-expression of the S100A2 gene in stage I NSCLC indicates a poor prognosis, and may be used to identify patients with early-stage NSCLC [39], or even as a predictor of distant metastasis [40].…”