1. ¹Gene Function Group, Roy Castle Lung Cancer Programme (Clinical Dental Sciences), University of Liverpool Cancer Research Centre, 200 London Road, Liverpool L3 9TA, UK
2. ²Institute of Pathology, University of Bern, 3010 Bern, Switzerland
3. ³Institute of Science and Technology in Medicine, Keele University School of Medicine, University Hospital of North Staffordshire, Stoke-on-Trent ST4 7QB, UK
4. ⁴Institute of Medical Oncology, University of Bern, 3010 Bern, Switzerland

Correspondence: Dr J Heighway, Roy Castle International Centre for Lung Cancer Research, University of Liverpool Cancer Research Centre, 200 London Road, Liverpool L3 9TA, UK. E-mail: heighwayj@roycastle.liv.ac.uk

Received 21 May 2004; Revised 22 July 2004; Accepted 16 August 2004; Published online 5 October 2004.

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 (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 Np63 transcript, the product of which is a putative regulator of S100A2 transcription and while all but one of the tumours positive for Np63 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).