Loss in 3p and 4p and Gain of 3q Are Concomitant Aberrations in Squamous Cell Carcinoma of the Vulva

Abstract

Neoplasm of the vulva is a rare malignancy accounting for <5% of all female genital-tract cancer. However, in recent years the incidence of vulva intraepithelial neoplasia, known to serve as a precursor to carcinoma, has increased in young women generating considerable interest in its pathogenesis. Genetic changes at the molecular level in precursor or invasive vulvar tumors are not well investigated, and DNA copy number changes have not been reported until now. We used comparative genomic hybridization (CGH) to analyze genetic alterations in 10 primary invasive squamous cell carcinomas of the vulva. Chromosomal aberrations were identified in 8/10 cases. The most frequent chromosomal losses were 4p13-pter (five cases), 3p (four cases), and 5q (two cases), and less frequent losses were detected at 6q, 11q, and 13q (one case each). The most frequent chromosomal gains were 3q (four cases) and 8p (three cases), and less frequent gains were found in 9p, 14, 17, and 20q (one case each). The pattern of chromosomal imbalance in vulvar cancer detected by CGH was revealed to be very similar to that in cervical cancers, despite regional differences in their prevalence. These results suggest that the pathogenic pathways in vulvar and cervical carcinomas may be similar and that the genetic background may be common to these two squamous cell carcinomas.

Genetic aberrations detected by comparative genomic hybridisation in vulvar cancers

“…Chromosome 3p loss has been previously documented in vulvar SCCs by LOH studies Pinto et al, 1999) and by CGH (Jee et al, 2001). The previous LOH studies indicate that the loss of 3p markers was not related to HPV status, which is supported by our own CGH data.…”

“…However, the HPV status of these cases was unreported. Whilst the majority of changes detected in this previous series is similar to our own, Jee et al (2001) found the commonest detectable change to be 4p loss (5 out of 10 cases). 4p loss was only detected in one of our 18 cases (an HPV-positive case).…”

“…Interestingly, one previous study of regions of genomic loss in vulvar cancer detected by LOH found only two of 11 cases to show loss of the 4p marker D4S2366 (Pinto et al, 1999). It is possible therefore that the difference in detection of this regional loss between our own study and that of Jee et al (2001) is due to the different demographics of the two populations studied, confounded by the small number of cases studied in each series and the probable relatively low incidence of 4p loss in vulvar cancers overall.…”

“…Further, we were able to map the smallest region of gain in vulvar SCCs to 3q22 -25, whilst our previous series of cervical cancers showed the smallest area of gain to be 3q24 -26 (Allen et al, 2000). Only one previous CGH analysis of vulvar carcinoma has been published, which detected 3q gain as the most common region of gain (40% of 10 cases) (Jee et al, 2001). However, these tumours were not assessed for HPV status.…”

“…Only one previous study describing CGH analysis of vulvar carcinomas has been published (Jee et al, 2001). However, the HPV status of these cases was unreported.…”