MOLECULAR-GENETIC TUMOR-MARKERS IN THE EARLY DIAGNOSIS AND SCREENING OF NON-SMALL-CELL LUNG-CANCER

Background: Little progress has been made in decreasing lung cancer mo rtality by applying conventional methods to early diagnosis and screen ing. Recent advances in molecular oncology, however, have provided too ls which may be of use in this area. Many genes involved in controllin g cell growth and differentiation are abnormal in lung cancer cells. S uch genes include K-ras, p53, rb, myc, her2/neu, and probably one or m ore tumor suppressor genes on chromosome 3p. The involvement of these genes in lung cancer is reviewed. The K-ras oncogene contains a mutati on in codon 12 in many cases of non-small-cell lung cancer, particular ly adenocarcinoma, and is thus a potentially useful lung cancer tumor marker. Design: We have developed a highly sensitive, simple assay for ras mutations, and applied it to bronchoalveolar lavage fluid obtaine d from patients undergoing evaluation for suspected lung cancer. Resul ts: In many cases, the ras assay was more sensitive than routine cytol ogy and histopathology, demonstrating that this is a potentially clini cally useful assay. Conclusion: Molecular genetic tumor markers, inclu ding mutations in ras and other genes, and/or immunohistochemical tumo r markers, may provide tools which can be applied to bronchoalveolar l avage fluid or sputum, for use in diagnostic tests and in screening pr ograms. The use of such markers may lead to decreased lung cancer mort ality.