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Molecular evidence of a common clonal origin and subsequent divergent clonal evolution in vulval intraepithelial neoplasia, vulval squamous cell carcinoma and lymph node metastases



Molecular evidence of a common clonal origin and subsequent divergent clonal evolution in vulval intraepithelial neoplasia, vulval squamous cell carcinoma and lymph node metastases



International Journal of Cancer 99(4): 549-554



VIN is thought to be the precursor of some VSCCs because it is monoclonal, frequently occurs contiguously with VSCC and shares similar risk factors with a subgroup of VSCC. There has been no conclusive molecular evidence supporting this assumption. We performed X-chromosome inactivation analysis on 9 cases of lone VIN, 10 cases of VSCC and associated contiguous VIN and 11 cases of VSCC and associated noncontiguous VIN. Eight of the 9 cases of lone VIN appeared to be monoclonal. All 7 informative and monoclonal cases of VIN with contiguous VSCC and 6/9 informative cases of VIN with noncontiguous VSCC showed patterns of X-chromosome inactivation consistent with a common monoclonal origin for both VIN and VSCC. Two of the 9 cases of VIN with noncontiguous VSCC showed X-chromosome inactivation patterns consistent with a separate clonal origin. We performed LOH analysis at 6 chromosomal loci on these samples and 7 cases with lymph node metastases. Identical losses occurred 7 times in VIN and contiguous VSCC (random probability 1.2 x 10(-9)), twice in VIN and noncontiguous VSCC (random probability 1.5 x 10(-3)) and 3 times in VSCC and associated metastases (random probability 1.8 x 10(-5)). Some losses occurring in VSCC did not appear in the contiguous VIN or associated metastases and vice versa. These data provide molecular evidence that VIN is the precursor of VIN-associated VSCC, that multifocal disease may arise via either different clones or a single clone and that continued divergent clonal evolution may occur in vulval neoplasia.

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Accession: 011007670

Download citation: RISBibTeXText

PMID: 11992544

DOI: 10.1002/ijc.10362


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