Associação de neoplasia escamosa intraepitelial e invasiva da vulva a infecção por papiloma virus humanos e a imunodetecção da proteina p53
Diana Elici Sader Engelman
TESE
Português
(Broch.)
T/UNICAMP En32a
Campinas, SP : [s.n.], 2001.
277p. : il.
Orientador : Jose Vassallo
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Resumo: o carcinomada vulva é ainda hoje uma doençade etiologiaindefinida.Estudosrecentesapontam para uma origem multifatorial onde os papilomavírushumanos (HPV) seriam os agentes responsáveis pelo desenvolvimentoda neoplasia vulvar em grupos etários mais jovens, enquanto que nas pacientes mais...
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Resumo: o carcinomada vulva é ainda hoje uma doençade etiologiaindefinida.Estudosrecentesapontam para uma origem multifatorial onde os papilomavírushumanos (HPV) seriam os agentes responsáveis pelo desenvolvimentoda neoplasia vulvar em grupos etários mais jovens, enquanto que nas pacientes mais idosas estaria provavelmente relacionada à presença de lesões distróficas, de mutações genéticas, além de outros fatores ainda pouco conhecidos. Tivemos como objetivo avaliar a presença do HPV e da proteína p53 e correlaciona-Ias com outros parâmetros clínico-patológicos nos grupos de pacientes com neoplasia intraepitelial vulvar (NN m - 38 casos), carcinoma superficialmente invasivo (nove casos) e carcinoma escamoso invasivo da vulva (55 casos). A detecção do HPV foi realizada através de exame imuno-histoquímico com o anticorpo anti-HPV policlonal e da hibridização molecular in situ com sondas biotiniladas de amplo espectro e para os tipos 6/11, 16/18 e 31/35/51. A proteína p53 foi identificada através de exame imuno-histoquímico com o anticorpo monoclonal DO-7. No grupo com NN m a idade média das pacientes foi de 47,5 anos; 45,7% tinham lesão de condiloma associado, o HPV estava presente em 57,9% dos casos e a proteína p53 em 21,1%. As pacientes com carcinoma superficialmente invasivo tinham idade média de 57,9 anos, lesão de condiloma em 22,2%, detecção do HPV em 33,3% e da proteína p53 em 66,7% dos casos. No carcinoma escamoso invasivo a idade média foi de 67,8 anos e apenas 7,3% das pacientes tinham lesão de condiloma associado; lesões distróficas estavam presentes em 60% dos casos e NN m em 25,5%; o HPV foi identificado em 7,3% e a proteína p53 em 58,2%. A detecção do HPV foi mais freqüente no grupo com lesão de NN m e estava relacionada à idade mais jovem das pacientes. No grupo com carcinoma invasivo, a variante histológica mais freqüente foi a queratinizante usual e estava associada à presença de lesões distróficas e da proteína p53. Entretanto, uma pequena subpopulação de pacientes mais jovens continham a variante basalóide do carcinoma invasivo, freqüentemente associada à lesão de NN m e à infecção pelo HPV. Os nossos resultados são semelhantes aos da literatura, onde um grupo de lesões está relacionado com a infecção pelo HPV e outro não. O HPV 16/18 foi o tipo predominanteem todos os grupos de lesões. Índices mais baixos de detecção da p53 nas lesões de NN m e maiores e com proporções semelhantes no carcinoma superficialmente invasivo e invasivo, além da ausência de relação entre a presença da p53 e do HPV, indicam que a imunodetecção da p53 é secundária à invasão do estroma pela neoplasia e é independente da presença de infecção viral. A detecção da proteína p53 estava associada apenas com a profundidade de invasão tumoral e não mostrou relação com neoplasia recidivante ou metástases ganglionares e, portanto, não tem valor como marcador para lesões recidivantes ou metastáticas, pelo menos para o grupo de pacientes incluídas neste trabalho
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Abstract: Vulvar squamous cell carcinoma still is a disease of unknown etiology. Recent studies have pointed out to a multifactorial origin, with HPV as the causal agent in the developrnentof vulvar neoplasia
in younger age groups, whereas in older patients it would be possibly related to dystrophic... Ver mais Abstract: Vulvar squamous cell carcinoma still is a disease of unknown etiology. Recent studies have pointed out to a multifactorial origin, with HPV as the causal agent in the developrnentof vulvar neoplasia
in younger age groups, whereas in older patients it would be possibly related to dystrophic lesions,genetic mutations, and other factors still unknown. Our purpose was to analyze the presence of HPV and p53 overexpression and correlate them with other clinical and pathological parameters in patients with vulvar intraepithelial neoplasia grade m (VIN m - 38 cases), superficially invasive carcinoma (nine cases), and invasive squamous cell carcinoma of the vulva (55 cases). HPV infection was determined by immunoperoxidase reaction with a policlonal antibody against HPV and by in situ hybridization with biotinilated probes for wide spectrum and HPV types 6/11, 16/18 and 31/35/51. P53 overexpression was detected by immunoperoxidasereaction with the monoclonal antibody DO-7. In the VIN m group, the mean age was 47.5 years; 45.7% had associated condylomatous lesions, HPV infection was detected in 57.9% ofthe cases, and p53 overexpression in 21.1%. The patients with superficially invasive carcinoma had mean age of 57.9 years, condylomatous lesions in 22.2%, HPV infection in 33.3%, and p53 overexpression in 66.7% ofthe cases. In the invasive squamous carcinoma group the mean age was 67.8 years; 7.3% ofthe patients had associated condylornatous lesions, 60% presented with dystrophic lesions and 25.5% with VIN m; HPV were identified in 7.3%, and p53 overexpression in 58.2% of the cases. Our findings
revealed that HPV detection occurred mainly in the VIN m group and was related to younger patients. In the invasive squamous carcinoma group, the most common histological variant was the
usual type of keratinizing squamous cell carcinoma, and it was associated to dystrophic lesions and p53 overexpression. However, a small subpopulation of younger patients contained the basaloid
type of invasive carcinoma, and it was :&equentlyassociated to VIN m lesions and HPV infection. Our results are similar to other reports, where two separate entities of the disease exist, one associated with HPV infection, and other unrelated to it. HPV 16/18 was the predominant type in all the three groups of lesions. The weakness or absence of p53 overexpression in VIN m lesions, and its higher detection, with stronger positivity and similar distribution in superficially invasive and invasive carcinoma, together with the lack of relationship between p53 overexpression and HPV infection, indicates that p53 overexpression is related to neoplastic stromal invasion and it is independent of HPV infection. P53 detection was associated only to the depth of stromal invasion and unrelated to tumor recurrence or lymph node metastasis and therefore, it had no significance as a prognostic marker, at least in the group of patients included in this study Ver menos
in younger age groups, whereas in older patients it would be possibly related to dystrophic... Ver mais Abstract: Vulvar squamous cell carcinoma still is a disease of unknown etiology. Recent studies have pointed out to a multifactorial origin, with HPV as the causal agent in the developrnentof vulvar neoplasia
in younger age groups, whereas in older patients it would be possibly related to dystrophic lesions,genetic mutations, and other factors still unknown. Our purpose was to analyze the presence of HPV and p53 overexpression and correlate them with other clinical and pathological parameters in patients with vulvar intraepithelial neoplasia grade m (VIN m - 38 cases), superficially invasive carcinoma (nine cases), and invasive squamous cell carcinoma of the vulva (55 cases). HPV infection was determined by immunoperoxidase reaction with a policlonal antibody against HPV and by in situ hybridization with biotinilated probes for wide spectrum and HPV types 6/11, 16/18 and 31/35/51. P53 overexpression was detected by immunoperoxidasereaction with the monoclonal antibody DO-7. In the VIN m group, the mean age was 47.5 years; 45.7% had associated condylomatous lesions, HPV infection was detected in 57.9% ofthe cases, and p53 overexpression in 21.1%. The patients with superficially invasive carcinoma had mean age of 57.9 years, condylomatous lesions in 22.2%, HPV infection in 33.3%, and p53 overexpression in 66.7% ofthe cases. In the invasive squamous carcinoma group the mean age was 67.8 years; 7.3% ofthe patients had associated condylornatous lesions, 60% presented with dystrophic lesions and 25.5% with VIN m; HPV were identified in 7.3%, and p53 overexpression in 58.2% of the cases. Our findings
revealed that HPV detection occurred mainly in the VIN m group and was related to younger patients. In the invasive squamous carcinoma group, the most common histological variant was the
usual type of keratinizing squamous cell carcinoma, and it was associated to dystrophic lesions and p53 overexpression. However, a small subpopulation of younger patients contained the basaloid
type of invasive carcinoma, and it was :&equentlyassociated to VIN m lesions and HPV infection. Our results are similar to other reports, where two separate entities of the disease exist, one associated with HPV infection, and other unrelated to it. HPV 16/18 was the predominant type in all the three groups of lesions. The weakness or absence of p53 overexpression in VIN m lesions, and its higher detection, with stronger positivity and similar distribution in superficially invasive and invasive carcinoma, together with the lack of relationship between p53 overexpression and HPV infection, indicates that p53 overexpression is related to neoplastic stromal invasion and it is independent of HPV infection. P53 detection was associated only to the depth of stromal invasion and unrelated to tumor recurrence or lymph node metastasis and therefore, it had no significance as a prognostic marker, at least in the group of patients included in this study Ver menos
Associação de neoplasia escamosa intraepitelial e invasiva da vulva a infecção por papiloma virus humanos e a imunodetecção da proteina p53
Diana Elici Sader Engelman
Associação de neoplasia escamosa intraepitelial e invasiva da vulva a infecção por papiloma virus humanos e a imunodetecção da proteina p53
Diana Elici Sader Engelman
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