High frequency of loss of heterozygosity in vulval intraepithelial neoplasia (VIN) is associated with invasive vulval squamous cell carcinoma (VSCC)

Authors

  • Adam N. Rosenthal,

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

    1. The Gynaecological Oncology Unit, St. Bartholomew's and the 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 the Royal London Hospitals Medical College, Queen Mary and Westfield College, London, United Kingdom
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  • Thirunavukarasu Surentheran,

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

    Corresponding author
    1. The Gynaecological Oncology Unit, St. Bartholomew's and the Royal London Hospitals Medical College, Queen Mary and Westfield College, London, United Kingdom
    • The Gynaecological Oncology Unit, St. Bartholomew's and the Royal London Hospitals Medical College, Queen Mary and Westfield College, West Smithfield, London EC1A 7BE, UK
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Abstract

Vulval intraepithelial neoplasia (VIN) is thought to be the premalignant phase of human papillomavirus (HPV)-associated vulval squamous cell carcinoma (VSCC). Various molecular events have been suggested as markers for progression from VIN to VSCC, but loss of heterozygosity (LOH) in vulval neoplasia has rarely been studied in this context. We performed LOH analysis by polymerase chain reaction (PCR) amplification of polymorphic microsatellite markers at 6 chromosomal loci (17p13-p53, 9p21-p16, 3p25, 4q21, 5p14 and 11p15). The presence of HPV was assessed using consensus PCR primers and DNA sequencing. To examine any association between LOH and the presence of invasive disease, we analyzed 43 cases of lone VIN III, 42 cases of lone VSCC and 21 cases of VIN with concurrent VSCC. HPV DNA was detected in 95% of lone VIN III samples and 71% of lone VSCC samples. Fractional regional allelic loss (FRL) in VIN associated with VSCC was higher than in lone VIN (mean FRL 0.43 vs. 0.21, p < 0.005). LOH at 3p25 occurred significantly more frequently in HPV-negative VSCC than in HPV-positive VSCC (58% vs. 22%, p < 0.04). These data suggest that genetic instability in VIN, reflected by LOH, may increase the risk of invasion. In addition, molecular events differ in HPV-positive and -negative VSCC and 3p25 may be the site of a tumor suppressor gene involved in HPV-independent vulval carcinogenesis. © 2001 Wiley-Liss, Inc.

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