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Early aberrant gene expression in primary non-small cell carcinomas: a future diagnostic tool?
  1. S E A Fairbairn
  1. Specialist Research Registrar, Department of Respiratory Medicine, Royal Gwent Hospital, South Wales, UK;

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The S100A2 gene has previously been shown by this group to be significantly increased in non-small cell lung cancer. This study examined the expression of S100A2 in primary non-small cell lung carcinomas (NSCLC) with matched normal bronchial epithelium. Tumour tissue was obtained from 48 patients (37 men, 11 women) with resectable NSCLC (20 squamous cell, 24 adenocarcinomas, three large cell, and one poorly differentiated NSCLC) and matched with normal bronchial epithelial tissue from a tumour-free site in all but two patients. Reverse transcriptase polymerase chain reactions and immunohistochemical analysis were used to quantify the expression of S100A2 and allow consideration of its association with tumour histology, clinical outcome, and pre-neoplasia.

S100A2 was detected in the normal tissue of most patients but it was also strongly overexpressed (>2-fold) in 76% of tumour tissues compared with matched controls. Squamous cell carcinomas expressed S100A2 more frequently than adenocarcinomas (p<0.002), but no correlation was found between gene expression and overall survival or smoking history. S100A2 expression was also shown to be increased in apical bronchial epithelial cells in association with an increase in the degree of cellular abnormality (p<0.0001). In contrast, basal bronchial epithelial cells exhibited strong expression of S100A2 in both tumour tissues and matched controls (97%). Supplemental analysis did not support previous identification of S100A2 as a tumour suppressor gene but did suggest a link between its expression and the transcriptional activator gene p63.

Early detectable gene expression in NSCLC may allow the future development of pre-symptomatic detection of lung cancer and therefore the opportunity for early therapeutic intervention leading to a significant reduction in lung cancer mortality.