Microsatellite instability and other molecular abnormalities in nonsmall cell lung-cancer

Microsatellites are highly polymorphic, short-tandem repeat sequences dispersed throughout the genome, Instability of these repeat sequences at multiple genetic loci may result from mismatch repair errors and occur in hereditary nonpolyposis colorectal carcinoma and certain sporadic cancers, In non-small cell lung cancer, we found that microsatellite instability was infrequent, affecting only 7 (6.5%) of 108 cases, Despite being observed in all histological subtypes and at different tumor stages, microsatellite instability most commonly affected only one of the six loci tested on five chromosomal arms, In addition, microsatellite instability was associated with extensive, concurrent molecular changes including K-ras and p53 mutations as well as frequent loss of heterozygosity at chromosomal regions 5q, 8p, 9p, 11p, and 17p

Exhaled breath analysis for lung cancer

Early diagnosis of lung cancer results in improved survival compared to diagnosis with more advanced disease. Early disease is not reliably indicated by symptoms. Because investigations such as bronchoscopy and needle biopsy have associated risks and substantial costs, they are not suitable for population screening. Hence new easily applicable tests, which can be used to screen individuals at risk, are required. Biomarker testing in exhaled breath samples is a simple, relatively inexpensive, non-invasive approach. Exhaled breath contains volatile and non-volatile organic compounds produced as end-products of metabolic processes and the composition of such compounds varies between healthy subjects and subjects with lung cancer. Many studies have analysed the patterns of these compounds in exhaled breath. In addition studies have also reported that the exhaled breath condensate (EBC) can reveal gene mutations or DNA abnormalities in patients with lung cancer. This review has summarised the scientific evidence demonstrating that lung cancer has distinct chemical profiles in exhaled breath and characteristic genetic changes in EBC. It is not yet possible to accurately identify individuals with lung cancer in at risk populations by any of these techniques. However, analysis of both volatile organic compounds in exhaled breath and of EBC have great potential to become clinically useful diagnostic and screening tools for early stage lung cancer detection

TIMP1 and adverse prognosis in non-small cell lung cancer

The tumor inhibitor of metalloproteinase (TIMP) family is a natural inhibitor of several matrix metalloproteinase enzymes which are involved in the process of tumor cell invasion through the extracellular matrix, The aim of this study was to examine TIMP1 RNA expression levels in relation to the clinicopathological features in resected primary non-small cell lung cancer (NSCLC), Total cellular RNA, obtained from 45 cases of NSCLC and adjacent normal lung tissue, was examined using Northern blot analysis, TIMP1 RNA expression levels were heterogeneous in NSCLC but was significantly higher in the adenocarcinoma compared to the squamous cell carcinoma subtype. Although the TIMP1 RNA levels did not correlate with sex, smoking, tumor, node, or TNM stage, there was a statistically significant survival disadvantage for cases with relatively high TIMP1 RNA expression, suggesting a role for TIMP1 in determining the prognosis of resected NSCLC

Loss of Heterozygosity frequently affects chromosome 17Q in non-small-cell lung-cancer

Although the short arm of chromosome 17, which contains the p53 gene, is frequently affected by loss of heterozygosity (LOH) in lung cancer, little is known about similar changes on the long arm. We found that LOH affected one or more of six loci along chromosome 17 in 59% of 102 informative non-small cell lung cancer (NSCLC) cases. Specifically, the frequency of LOH at 17q was 42%, approaching that at 17p (54%), and two distinct 17q regions were implicated. LOH at D17S4 on 17q was more frequent in adenocarcinomas than in squamous cell carcinomas, whereas squamous cell carcinomas had more LOH at 17p than at 17q, findings that indicate molecular genetic heterogeneity between the major NSCLC subtypes. In addition, LOH at 17q correlated with higher T stages and a significantly worse prognosis. In comparison, 25% of cases had mutations of p53 exons 5-8 but these were not associated with stage or survival. The data suggest that independent of p53, there are important tumor suppressor gene(s) on 17q that may influence NSCLC pathogenesis, progression, and survival