Detection of Microsatellite Alterations in Bronchial Washings in Squamous Cell Lung Cancer: the First Study from India

Abstract

Background: In recent times, the possibility of detecting lung cancer using microsatellite alterations (microsatellite instability and loss of heterozygosity) in DNA of bronchial washings has been explored. However, no data regarding the presence of microsatellite alterations in lung cancer are available from India, a country which contributes significantly to the lung cancer burden of the world. Methods: Bronchial washings as well as tumor specimens obtained on bronchoscopy were analyzed for the presence of loss of heterozygosity (LOH) and microsatellite instability (MSI) using the D3S1300 microsatellite marker on chromosome 3p and the TP53 marker on chromosome 17p. Results: The sensitivities of the TP53 and D3S1300 loci in bronchial washings were 35% and 45% (combined 50%), respectively, which was significantly better than conventional cytology (positive for malignant cells in 15%). The presence of these microsatellite alterations was not related to the age, cumulative smoking exposure or smoking status (current or former) of patients. Conclusion: Microsatellite alterations, particularly LOH, occur in a significant proportion of Indian patients with squamous cell carcinoma of the lung.

Analysis of microsatellite mutations in buccal cells from a case-control study for lung cancer

“…This includes a study on chronic obstructive pulmonary disease (COPD) that, while finding no mutations in healthy nonsmokers, also noted no statistically significant association between smoking status and MSI [35]. An investigation of squamous cell carcinoma of the lung concluded that MSI did not seem to be related to cumulative smoking exposure or smoking status [28]. Our study also failed to find any significant correlation between smoking status and mutation frequency in normal buccal epithelium.…”

“…When assessed in larger cell populations, these mutations are detectable as microsatellite instability (MSI), whereas our small-pool PCR approach is capable of characterizing mutations at the individual molecule level which allows precise quantitation of the mutational load. The ability to measure microsatellite mutations in cells obtained from buccal rinses [18], sputum samples [27], other noninvasive sampling techniques and from bronchial washings [28], allows the study of genomic alterations in tissues exposed to tobacco carcinogens. This study is the first of its kind to evaluate how mutations in the highly mutable tetranucleotide markers MycL1, D7S1482 and DXS981 relates to age, smoking status, and cancer status in DNA obtained from buccal rinses of patients suspected of lung carcinoma.…”

Genetic Instability in Peripheral Lymphocytes as Biological Marker for Non-Small Cell Lung Cancer Patients in the South Indian State of Andhra Pradesh

“…It is believed that squamous cell carcinoma was the predominant form of NSCLC until the 1970's, and that there has been a shift in the pathological features of NSCLC, with adenocarcinoma becoming the more frequent pathological subtype (48). Furthermore, until 2004, in the Indian context the incidence of squamous cell carcinoma seemed to be predominant (49, 50). Based on the results obtained in this study, it is possible that the pathological shift could be now happening in the Andhra Pradesh population.…”

Loss of Fragile Histidine Triad Gene Expression in Advanced Lung Cancer Is Consequent to Allelic Loss at 3p14 Locus and Promoter Methylation

“…Hence, LOH studies on cell sediments of the bronchoalveolar lavage fluid can supplement conventional cytologic techniques for detection of malignancy. In a previous study, it has been shown that the sensitivity of cytologic detection can be improved by LOH analysis using D3S1300 marker (19). In two cases, LOH was detected in the bronchoalveolar lavage fluid samples but not in the tumor biopsies.…”