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

• Published in: British journal of cancer Vol. 91; no. 8; pp. 1515 - 1524
• Main Authors: SMITH, S. L, GUGGER, M, HOBAN, P, RATSCHILLER, D, WATSON, S. G, FIELD, J. K, BETTICHER, D. C, HEIGHWAY, J
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 18.10.2004
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adult; Aged; Aged, 80 and over; Allelic Imbalance; Biological and medical sciences; Biomarkers, Tumor - metabolism; Bronchi - metabolism; Bronchi - pathology; Cancer research; Carcinoma, Large Cell - genetics; Carcinoma, Large Cell - metabolism; Carcinoma, Large Cell - pathology; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Chemotactic Factors - genetics; Chemotactic Factors - metabolism; Disease; DNA-Binding Proteins; Epithelial Cells - metabolism; Epithelial Cells - pathology; Female; Gene Amplification; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Head & neck cancer; Humans; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Medical research; Medical sciences; Middle Aged; Molecular and Cellular Pathology; Neoplasms, Basal Cell - genetics; Neoplasms, Basal Cell - metabolism; Neoplasms, Basal Cell - pathology; Phosphoproteins - metabolism; Pneumology; Precancerous Conditions - metabolism; Precancerous Conditions - pathology; S100 Proteins - genetics; S100 Proteins - metabolism; Trans-Activators - metabolism; Transcription Factors; Tumor Suppressor Proteins; Tumors; Tumors of the respiratory system and mediastinum; United Kingdom > UK; Lung disease; preneoplasia; Premalignant lesion; expression; S100A2; Respiratory disease; Lung cancer; Malignant tumor; non-small cell lung carcinoma; Respiratory system; Respiratory tract; lung; Cancerology; carcinoma; Primary; Bronchus disease
• ISSN: 0007-0920; 1532-1827
• 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).