p53 Protein Expression in a Population-Based Series of Primary Vulval Squamous Cell Carcinoma and Immediate Adjacent Field Change

McConnell, Dynes T.; Miller, Iain D.; Parkin, David E.; Murray, Graeme I.

doi:10.1006/gyno.1997.4862

Cited by 29 publications

(34 citation statements)

References 16 publications

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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%

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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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Section: Discussionmentioning

confidence: 99%

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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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“…In order to reduce surgical morbidity, to identify which patients will develop recurrent disease and metastasis, several prognostic markers have been proposed, including p53 (12,25,26). There are also studies investigating its role as a predictor of radiotherapy and chemotherapy resistance (7,25).…”

Section: Discussionmentioning

confidence: 99%

Human papillomavirus infection and p53 protein expression in vulvar intraepithelial neoplasia and invasive squamous cell carcinoma

Engelman

Andrade

Vassallo

2003

Braz J Med Biol Res

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The etiopathogenesis of vulvar intraepithelial neoplasia (VIN III) and invasive squamous cell carcinoma are largely unknown. Since there are few studies on Brazilian patients, our purpose was to determine the frequency of human papillomavirus (HPV) infection and the expression of p53 in these lesions, and associate them with other factors such as age, morphological subtypes, multicentric and multifocal disease. Thirty-eight cases of VIN III, nine of superficially invasive carcinoma, and 55 of invasive vulvar carcinoma were retrospectively evaluated from 1983 to 1995 for the presence of HPV by immunohistochemistry and in situ hybridization, and for p53 protein expression by immunohistochemistry on paraffin sections. All cases for whom material (slides and paraffin blocks) and clinical data were available were included. HPV and p53 were detected in 57.9 and 21.1% of the VIN III lesions, 33.3 and 66.7% of superficially invasive carcinomas, and 7.3 and 58.2% of invasive squamous cell carcinomas, respectively. HPV infection was associated with younger age in the VIN III and invasive carcinoma groups. In the latter, HPV infection was associated with the basaloid variant. p53 expression rate was higher in superficially invasive and invasive lesions and was not related to HPV infection. Our findings are similar to others and support the hypothesis that there are two separate entities of the disease, one associated with HPV and the other unrelated, with p53 inactivation possibly being implicated in some of the cases. Correspondence

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“…The loci studied were chosen for specific reasons: 17p13 because it harbors p53, which accumulates in 53-68% of VSCC 13,14 and 9p21 (p16 gene) and 3p25 because they frequently exhibit LOH in squamous head and neck cancer. [15][16][17] p16 is also disrupted in VIN and VSCC.…”

Section: Discussionmentioning

confidence: 99%

“…p53 may be involved in progression from VIN to VSCC as p53 product accumulated in 53% of VSCCs (n ϭ 66) 13 and 44% (n ϭ 34) 14 of VIN associated with VSCC, but 0% of VIN not associated with VSCC (n ϭ 28). 4 In our series, the p53 locus was lost more in VSCC(ϩ) than in VIN(ϩ), which in turn had more loss of p53 than VIN(Ϫ) (Fig.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2001

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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. Key words: VIN; vulval; cancer; LOH; HPVVulval intraepithelial neoplasia (VIN) is thought to be the premalignant phase of invasive vulval squamous cell carcinoma (VSCC). This hypothesis is based on the observation that VIN frequently occurs adjacent to VSCC, 1 that VIN and a subgroup of VSCC are associated with similar risk factors [smoking, 2 immunosuppression 3 and human papillomavirus (HPV) infection 2,4 ] and that VIN is a monoclonal neoplastic condition. 5 The risk of progression of VIN to VSCC is unclear. 6,7 Limited evidence is available about molecular events in vulval carcinogenesis. Loss of heterozygosity (LOH) is a common molecular event in malignancy, but has been studied only in relatively small numbers of VIN and VSCC. 8 -11 We set out to document the LOH rates in VIN and VSCC in a larger series, to examine the relationship between the 2 conditions. Events common to both conditions could be early events in vulval carcinogenesis. Events occurring in VIN associated with VSCC but not in lone VIN could be markers for risk of progression to VSCC.Because human papillomavirus (HPV) is thought to be involved in the development of VIN-associated VSCC, but is not found so often in VSCC occurring in the absence of VIN, 2 we also performed HPV analysis, to compare LOH in HPV-positive and HPV-negative VSCC. MATERIAL AND METHODS SamplesPatients with VIN and VSCC diagnosed between 1989 and 1997 were identified using the computerized database of the pathology departments of St. Bartholomew's and the Royal London Hospitals. Samples containing both normal and neoplastic tissue were as follows: 43 cases of VIN III alone, 42 cases of VSCC alone and 21 cases of VIN associated with concurrent VSCC (18 of which had the concurrent VSCC still remaining on the specimen blocks after serial sectioning). Of the 60 VSCC cases, 24 were stage I, 11 were stage II, 9 were stage III, 3 were stage IV and in 13 information for accurate staging was not available. Of the 21 cases of VIN associated with VSCC, 18 were VIN III, 2 were VIN II and 1 was VIN

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p53 Protein Expression in a Population-Based Series of Primary Vulval Squamous Cell Carcinoma and Immediate Adjacent Field Change

Cited by 29 publications

References 16 publications

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

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

Human papillomavirus infection and p53 protein expression in vulvar intraepithelial neoplasia and invasive squamous cell carcinoma

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

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