Genetic alterations in gallbladder adenoma, dysplasia and carcinoma

Adenoma and dysplasia in the gallbladder (GB) have been reported as precanc erous lesions, but the genetic evidence of this is not clearly defined. The purpose of this study was to analyze the frequencies of K-ras, p53, and p1 6 gene mutations, of microsatellite instability (MI) and of loss of heteroz ygosity (LOH) in GB cancer, dysplasia, and adenoma. Tissues from 15 GB canc ers, five dysplasias around cancerous tumors, and three adenomas were colle cted prospectively. The mutation rates of Kms, p53, and p16 were 20.0, 35.7 , and 30.7%, respectively, in GB cancers. However, no mutations were found in dysplasia or adenoma, Reduced staining for p16 was seen in 23% of carcin omas. All of the GB carcinomas and four out of five (80%) of the dysplasias showed LOH ill a minimum of one locus, hut one out of three (33%) cases of adenoma displayed LOH in only one locus. All of the loci of LOW in the dys plasias, except one, showed the same patterns of allelic loss as the adjace nt carcinomas. Only one dysplasia showed multiple MI. Tn conclusion, multip le LOH may be associated with the development of dysplasia and the malignan t transformation of GB carcinoma. Gene alterations of K-ms, p53, and p16 ar e important steps in the malignant changes of dysplasia. However, MI seems to have only a limited role in GB cancer development. (C) 2001 Elsevier Sci ence Ireland Ltd. All rights reserved.