Clear-cell adenofibroma can be a clonal precursor for clear-cell adenocarcinoma of the ovary: a possible alternative ovarian clear-cell carcinogenic pathway.

Several studies have reported that ovarian clear-cell adenocarcinoma can be derived from endometriosis. Although the clear-cell adenofibroma (CCAF), a major form of benign and borderline ovarian clear-cell tumour, has been suggested as another precursor for clear-cell adenocarcinoma (CCA), there is no supportive genetic evidence for this presumption. To examine the genetic linkage between CCAF and CCA of the ovary, we conducted allelotype analysis for both CCAF and adjacent CCA components in 14 cases of CCA associated with benign CCAF and/or borderline CCAF. DNA isolated from laser-microdissected tissue was subjected to polymerase chain reaction and analysis for loss of heterozygosity (LOH), using 17 polymorphic markers located on 11 chromosomal arms: 1p, 5q, 8p, 9p, 9q, 10q, 11q, 13q, 18q, 19p and 22q. For all informative loci, the frequency of LOH in adenocarcinoma was 49% (54/110 loci), and was significantly higher than those in the components of benign CCAF (22%, 20/92 loci) and borderline CCAF (30%, 25/83 loci) (chi(2) test; p<0.05, respectively). The concordance rate in allelic patterns at all informative loci was 74% between benign CCAF and adenocarcinoma components, 81% between borderline CCAF and adenocarcinoma components, and 95% between benign CCAF and borderline CCAF components. Furthermore, between CCAF and adenocarcinoma components, an identical LOH pattern, involving the same alleles, was found in 13 (93%) of 14 cases at one or more chromosomal loci, and estimation of probability indicated that these events were very unlikely to have occurred by chance. Among the markers examined, LOHs on 5q, 10q and 22q were frequent in both CCAF and adenocarcinoma components, whereas LOHs on 1p and 13q were rare in CCAF components but frequent in adenocarcinoma components. These findings suggest that CCAF can be a clonal precursor for ovarian clear-cell adenocarcinoma.