Genetic classification of combined hepatocellular-cholangiocarcinoma

Combined hepatocellular-cholangiocarcinoma (combined HCC/CC) is a rare form of liver neoplasms showing both hepatocellular (HCC) and bile duct differe ntiation (CC). In an attempt to clarify the clonality and genetic/phenotypi c relationships in the evolution of these neoplasms, we microdissected mult iple HCC and CC foci and studied allelic static; of chromosome arms 1p, 1q, 3p, 4q, 5q, 6q, 8p, 9p, 10q, 11q, 13q, 16q, 17p, 17q, 18q, and 22q. Overal l, the highest frequency of loss of heterozygosity (LOW) was seen on 4q and 17p, followed by 8p and 16q. Of the 11 cases studied, 3 cases did not show any of the identical allelic losses between HCC and CC foci, indicating th e biclonal nature. The remaining 8 cases showed multiple allelic losses sha red between bath components, strongly suggestive of a single clonal derivat ion. Moreover, 4 of the 8 cases showed additional or divergent allelic loss es at more than 1 chromosomal locus only in HCC and/or CC foci. Thus, this heterogeneity was shown to affect the phenotypic diversity of the tumor. Su mmarizing the genetic patterns, combined HCC/CC could be classified into th e following 3 possibilities: (1) collision tumor in which 2 independent neo plastic clones develop at dose proximity; (2) single clonal tumor with homo geneous genetic background in both components-histological diversity is thu s a manifestation of divergent differentiation potential of a single clone; (3) single clonal process in which genetic heterogeneity in the process of clonal evolution within the tumor parallels histologic diversity; therefor e, the tumor in this category is mainly composed of mosaics of closely rela ted subclones. Copyright (C) 2000 by W.B. Saunders Company.