[Molecular analysis of biopsies of bronchial cancers: feasibility of a systematic approach]

Malignant cells can be distinguished from their normal counterpart at the DNA level: they carry molecular changes which are characteristic of the tumor type or which might have some prognostic value. Amplifications and mutations of oncogenes and loss of alleles have been reported to occur in lung cancers, but their prognostic value has not yet been estimated, mainly for technical reasons: primary fresh biopsies are usually too small for molecular investigation. From 79 biopsies (50 of which were obtained by fiberoptic bronchoscopy), DNA hybridization was performed using the Southern blot technique, with myc family genes probes and a polymorphic probe located on the short arm of chromosome 3. Our study indicates that: 1) in 88% cases, enough DNA can be obtained by 3 or 4 fiberoptic bronchoscopy biopsies: from 5 to 80 micrograms DNA with an average of 25; 2) the quality of DNA is good for analysis by the Southern blot technique; 3) the loss of allele on chromosome 3 (3p 14-23) can be detected both in the small cell and in the non small cell type, but contamination of the specimens by non-tumoral tissue (based on the cytological and histological analysis of each biopsy) remains a problem for this type of study; 4) gene amplifications and rearrangements can be easily evaluated for the genes of the myc family. This pilot study shows that DNA analysis is feasible on perendoscopic biopsies. Collection and analysis of a large series of such biopsies at diagnosis is essential to define the value of DNA markers as prognostic factors in lung cancers.