Genetic changes in contralateral bronchioloalveolar carcinomas of the lung

Objective: The pattern of metastases and recurrence of bronchioloalveolar c arcinoma (BAC) differs from adenocarcinoma of the lung, occurring more freq uently within the lung without extrapulmonary involvement. Analyses of gene tic differences of contralateral BACs may help to explain these clinical di fferences. Methods: We compared paired tumors from 5 patients with contrala teral metachronous BACs for loss of heterozygosity (LOH) on 6 chromosomal a rms (2q, 3p, 5q, 9p, 13q and 17p) and mutational analysis of p53 and K-ras. Results: Two patients, patients 1 and 2, had discordant patterns of LOH on 2 and 3 of the chromosome arms, respectively. in addition, patient 2 had a detectable K-ras mutation in his initial tumor but not in his second. Thes e results suggest that in patients 1 and 2, the contralateral tumors were c lonally unrelated. Patient 3 had no mutations in the K-ras or p53 gene and no LOH on any of the 5 informative chromosome arms. Patient 4 had LOH of 9p and mutated K-ras in both the fi rst and the second tu mor, with a mutatio n in the p53 gene in the first but not in the second tumor. Patient 5 had L OH of 17p and the same p53 mutations in both the first and the second tumor , with a mutation of K-ras in the first tumor but not in the second. Conclu sions: The preponderance of evidence suggests that in patients 3, 4 and 5, the paired tumors were clonally related. The different patterns of LOH and mutations in clinically similar contralateral metachronous BACs provide evi dence of genetic heterogeneity in the tumors of this patient group. Copyrig ht (C) 2001 S. Karger AG, Basel.