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

Authors

  • Adam N. Rosenthal,

    1. Gynaecological Oncology Unit, St. Bartholomew's and Royal London Hospitals Medical College, Queen Mary and Westfield College, London, United Kingdom
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  • Andy Ryan,

    1. Gynaecological Oncology Unit, St. Bartholomew's and Royal London Hospitals Medical College, Queen Mary and Westfield College, London, United Kingdom
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  • Deborah Hopster,

    1. Academic Department of Histopathology, St. Bartholomew's and Royal London Hospitals Medical College, Queen Mary and Westfield College, London, United Kingdom
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  • Ian J. Jacobs

    Corresponding author
    1. Gynaecological Oncology Unit, St. Bartholomew's and Royal London Hospitals Medical College, Queen Mary and Westfield College, London, United Kingdom
    • Gynaecological Oncology Unit, St. Bartholomew's and Royal London Hospitals Medical College, Charterhouse Square, London EC1M 6GM, UK
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Abstract

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 × 10–9), twice in VIN and noncontiguous VSCC (random probability 1.5 × 10–3) and 3 times in VSCC and associated metastases (random probability 1.8 × 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. © 2002 Wiley-Liss, Inc.

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