3p Microsatellite Alterations in Exhaled Breath Condensate from Patients with Non–Small Cell Lung Cancer

Abstract

The still-high mortality for lung cancer urgently requires the availability of new, noninvasive diagnostic tools for use in early diagnosis and screening programs. Recently, exhaled breath condensate (EBC) has been proposed as a useful tool to obtain biological information on lung cancer disease. This study provides, for the first time, evidence that DNA alterations already described in lung cancer are detectable in EBC from patients with non-small cell lung cancer (NSCLC) and in healthy subjects. Thirty patients with histologic evidence of NSCLC and 20 healthy subjects were enrolled in the present study. All subjects had allelotyping analysis of DNA from EBC (EBC-DNA) and from whole blood (WB-DNA) of a selected panel of five microsatellites (D3S2338, D3S1266, D3S1300, D3S1304, D3S1289) located in chromosomal region 3p. Results from healthy subjects and subjects with cancer, and from EBC and WB, were compared. In addition, the relationships with smoking habit and clinicopathologic tumor features were considered. Microsatellite alterations (MAs) were found in 53% of EBC-DNA and in 10% of WB-DNA loci investigated in patients with NSCLC (p < 10(-6)); conversely, MAs were present only in 13% of EBC-DNA and in 2% of WB-DNA informative loci in healthy subjects. In patients with NSCLC, a direct association between number of MAs detected in EBC-DNA and tobacco consumption was observed. We conclude that EBC-DNA is highly sensitive in detecting MA information unique to patients with lung cancer. Furthermore, MA information seems to be directly related with tobacco consumption, and is potentially applicable to screening and early diagnostic programs for patients with NSCLC.

Exhaled breath condensate: a comprehensive update

“…It has been reported that a significantly greater proportion of patients with non-small cell lung cancer have 3p microsatellite alterations or loss of heterozygosity in EBC compared to controls [ 173 ], with overlapping profiles of microsatellite alterations in DNA from EBC and tumour tissues [ 174 ]. It has also been demonstrated that p53 mutations are present in EBC of patients with lung cancer, while no mutations were found in controls [ 175 ].…”

Exhaled breath condensate is not suitable to detect EGFR somatic mutations

“…gefitinib or erlotinib) has been stressed [1,2]. Interestingly, our group has already shown that the exhaled breath condensate (EBC) can be a useful and noninvasive way to collect biological samples derived from high up and deep within the airways [3,4]. EBC has been demonstrated to be informative on molecular alterations of nonsmall cell lung cancer (NSCLC) and to characterise the oxidative and inflammatory process in the airways/lung [5,6].…”

Neurokinin-1 Receptor Blockade and Murine Lung Tumorigenesis

“…In particular, staining for proliferation cell nuclear antigen marker and Ki-67 proliferation marker increases with increasing atypia when a decrease of the tumor suppressor factor FHIT is demonstrated. The latter factor has been involved in tumor initiation and progression of several cancers including those of the lung (33). In addition, the progressive accumulation of p53 expression does not parallel the expression of another member of the p53 signaling pathway, namely p21.…”