In squamous cell carcinoma of the vulva, overexpression of p53 is a late event and neither p53 nor mdm2 expression is a useful marker to predict lymph node metastases

The aim of this study was to review the literature on currently available non- and minimally-invasive diagnostic methods and analysis of primary tumor characteristics for prediction of inguinofemoral lymph node metastases in patients with primary squamous cell carcinoma of the vulva. We used the English language literature in Pubmed and reference lists from selected articles. Search terms included vulvar carcinoma, prognosis, lymph node metastases, ultrasound, computer tomography, magnetic resonance imaging, positron emission tomography, and sentinel lymph node. No study type restrictions were imposed. Currently no noninvasive imaging techniques exist that are able to predict lymph node metastases with a high enough negative predictive value. A depth of invasion ≤1 mm is the only histopathologic parameter that can exclude patients for complete inguinofemoral lymphadenectomy. No other clinicopathologic parameter allows exclusion of lymph node metastases with a high enough negative predictive value. The minimally invasive sentinel node procedure is a promising technique for selecting patients for complete lymphadenectomy, but its safety has not been proven yet.

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“…No relation was found between overexpression of p53 in the primary tumor and lymph node metastases in patients with vulvar carcinoma (70,76,77) .…”

Section: Cell Biologic Parametersmentioning

confidence: 92%

“…Overexpression of the tumor suppressor gene p53 in squamous cell vulvar carcinomas varies from 39% to 61% in different studies (74)(75)(76)(77)(78)(79)(80) . No relation was found between overexpression of p53 in the primary tumor and lymph node metastases in patients with vulvar carcinoma (70,76,77) .…”

Section: Cell Biologic Parametersmentioning

confidence: 99%

Prediction of lymph node metastases in vulvar cancer: a review

Oonk

Hollema

Hullu³

et al. 2006

Int J Gynecol Cancer

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“…We are aware of 11 studies that have examined p53 disruption in HPV-typed vulval neoplasia (Kurvinen et al, 1993;Tervahauta et al, 1993;Lee et al, 1994;Milde-Langosch et al, 1995;Pilotti et al, 1995;Kim et al, 1996;Kagie et al, 1997a, b;Kohlberger et al, 1998;Flowers et al, 1999;Ngan et al, 1999). A further four studies (McConnell et al, 1997;Sliutz et al, 1997;Emanuels et al, 1999;Scheistren et al, 1999) failed to examine HPV status, but two of these included VIN samples (McConnell Emanuels et al, 1999). Combining the data from these studies and our own, it appears that VIN associated with VSCC is significantly more likely to demonstrate aberrant p53 function than lone VIN (Table 5, 25 vs 7%, Po0.0004), suggesting that p53 could be a marker to identify women at risk of progression from VIN to VSCC.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies suggest absent p53 immunoreactivity in lone VIN (Kurvinen et al, 1993;Tervahauta Received 3 October 2002;accepted 9 October 2002accepted 9 October et al, 1993Pilotti et al, 1995;Kohlberger et al, 1998), while others have found 17 -52% p53 immunoreactivity in VIN associated with VSCC (Milde-Langosch et al, 1995;Kagie et al, 1997a ,b;McConnell et al, 1997;Emanuels et al, 1999). It is therefore possible that p53 immunoreactivity could represent a marker for risk of invasion.…”

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confidence: 99%

Immunohistochemical analysis of p53 in vulval intraepithelial neoplasia and vulval squamous cell carcinoma

et al. 2003

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Human papillomavirus (HPV) is thought to cause some vulval squamous cell carcinomas (VSCC) by degrading p53 product. Evidence on whether HPV-negative VSCC results from p53 mutation is conflicting. We performed immunohistochemistry for p53 product on 52 cases of lone vulval intraepithelial neoplasia (VIN), 21 cases of VIN with concurrent VSCC and 67 cases of VSCC. We had previously performed HPV detection and loss of heterozygosity (LOH) analyses on these samples. Abnormal p53 immunoreactivity (p53-positive) rates in HPV-positive VSCC and HPV-negative VSCC were 22% (12/54) and 31% (4/13), respectively (Po0.74). p53 immunoreactivity was associated with LOH at the p53 locus (Po0.004), but neither technique differentiated between HPV-positive and HPV-negative VSCC. p53 immunoreactivity was associated with overall LOH rates (p53-positive VSCC vs p53-negative VSCC mean fractional regional allelic loss 0.41 vs 0.24, respectively, Po0.027). LOH at 3p25 was more frequent in p53-positive VSCC cf p53-negative VSCC (70 vs 21%, respectively, Po0.007). There was a trend in p53 disruption associated with invasive disease; HPVpositive VSCC demonstrated more disruption than VIN associated with VSCC, which had more disruption than lone VIN III (22 vs 10 vs 0%, respectively, Po0.005). In all, three out of 73 cases of VIN were p53-positive. All three were associated with concurrent or previous VSCC. Meta-analysis of previous studies revealed significantly more p53 disruption in HPV-negative VSCC cf HPV-positive VSCC (58 vs 33%, respectively; Po0.0001). p53 immunoreactivity/mutation in VIN only appeared in association with VSCC. These data suggest that HPV-independent vulval carcinogenesis does not exclusively require disruption of p53, p53 disruption may work synergistically with LOH at specific loci and p53-positive VIN should be checked carefully for the presence of occult invasion.

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“…Many reports show that alterations in p53 may affect the carcinogenesis of the vulva more than that of the cervix, in which HPV infection predominates as a causative agent (3)(4)(5)(6). More recent data suggest that the overexpression of p53 protein is a late event and that the gene is a useful marker to predict lymph node metastasis in squamous cell carcinoma (7)(8)(9)(10).…”

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confidence: 99%

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

Jee

Kim

et al. 2001

Modern Pathology

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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.

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In squamous cell carcinoma of the vulva, overexpression of p53 is a late event and neither p53 nor mdm2 expression is a useful marker to predict lymph node metastases

Cited by 23 publications

References 28 publications

Prediction of lymph node metastases in vulvar cancer: a review

Prediction of lymph node metastases in vulvar cancer: a review

Immunohistochemical analysis of p53 in vulval intraepithelial neoplasia and vulval squamous cell carcinoma

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

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