Claudins and p53 expression in vulvar lichen sclerosus and squamous cell carcinoma

INTRODUÇÃO: O carcinoma escamoso (CEC) de vulva é um tumor ginecológico de baixa frequência, cuja incidência aumenta com o passar dos anos. Entre as vias patogenéticas, destaca-se a neoplasia intraepitelial vulvar (NIV) diferenciada, que está relacionada com o líquen escleroso (LE). A maioria dos estudos publicados comparou o CEC vulvar com LE no âmbito morfológico apenas. Poucos avaliaram estas afecções em relação à biologia molecular, e nenhum avaliou o papel da junção intercelular (TJ). Nosso objetivo foi analisar a expressão de claudinas (proteínas atuantes na TJ) e do p53 nestas doenças. CASUÍSTICA E MÉTODOS: avaliamos o produto do oncogene TP53 e a expressão das claudinas 1, 2, 3, 4, 5, 7 e 11 em amostras de tecido vulvar humano de três grupos de pacientes: LE, CEC isolado (ICEC) e grupo controle. RESULTADOS: As claudinas 1, 2, 3 e 4 foram expressas igualmente nos três grupos. As claudinas 5, 7 e 11 não foram expressas nos grupos LE e ICEC, estando presentes apenas no grupo controle. Esta diferença foi significativa apenas para as claudinas 7 (p=0,013) e 11 (p=0,001). A proteína p53 foi mais expressa no grupo ICEC, seguida pelo LE e pelo grupo controle (p=0,017). CONCLUSÕES: As claudinas 5, 7 e 11 não se expressaram nos casos de LE e/ou ICEC. As claudinas 7 e 11 foram expressas apenas no grupo controle. Houve perda da expressão das claudinas 7 e 11 nos grupos com doença (LE e ICEC), em comparação ao grupo controle. Não houve diferença na expressão de claudinas entre os grupos LE e ICEC. Observou-se presença de p53 nos grupos estudados, cuja distribuição variou conforme o grupo analisado. Esta expressão foi maior no grupo ICEC, seguido pelo LE e, menor, no grupo controleAIMS: Vulvar squamous cell carcinoma (SCC) is a rare gynaecologic cancer. Vulvar SCC has been shown to develop from vulvar intraepithelial neoplasias (VINs), which are related to lichen sclerosus (LS). Most studies to date have compared vulvar SCC to LS only morphologically, but no detailed molecular analysis has been performed. Our objective was to compare claudin and p53 expression in these diseases and determine if there was an association with expression and vulvar SCC progression. METHODS: Immunohistochemical analysis was performed in order to determine expression of p53 and claudin 1, 2, 3, 4, 5, 7, and 11 in human vulvar tissue samples from LS, SCC, and control patients. RESULTS: Claudin 1, 2, 3, 4, and 5 were expressed comparably in the three groups. Claudin 7 and 11 expression was significantly decreased in LS and SCC samples (p=0,013 and 0,001, respectively) compared with the control group. Expression of p53 was significantly increased in SCC and LS patient samples compared with the control group (p=0,017). CONCLUSIONS: Claudins 7 and 11 were expressed only in control group. There was loss of expression of claudins 7 and 11 in the disease groups (LS and/or SCC), comparing to control group. However, there was no significant difference in expression of any of the claudins between the LS and SCC samples. Furthermore, p53 expression is higher in SCC patients and lower in control group. However, expression of p53 did not vary between samples from isolated LS (ILS) and LS associated with SCC (ALSSCC) patient

Multiple HPV genotype infection impact on invasive cervical cancer presentation and survival

<div><p>Background</p><p>Invasive cervical cancer (ICC) is the third most common malignant neoplasm affecting Brazilian women. Little is known about the impact of specific HPV genotypes in the prognosis of ICC. We hypothesized that HPV genotype would impact ICC clinical presentation and survival.</p><p>Methods</p><p>Women diagnosed with ICC at the Instituto do Câncer do Estado de São Paulo (ICESP) between May 2008 and June 2012 were included in the study and were followed until December 2015. HPV genotype was detected from formalin-fixed paraffin-embedded (FFPE) tumor tissue samples using Onclarity™ system (BD Viper™ LT automated system).</p><p>Results</p><p>292 patients aged 50±14 years were analyzed. HPVDNA was detected in 84% of patients. The HPV genotypes studied were: HPV16 (64%), HPV18 (10%), HPV33-58 (7%), HPV45 (5%), HPV31 (4%) and other high-risk HPV genotypes (11%). HPV genotypes showed different distributions regarding histological type and clinical stage. Patients were followed for 35±21 months. The overall survival at 5 years after diagnosis of cervical cancer was 54%. Age, clinical staging, histological type and multiple HPV genotypes infection detected in the same tumor specimen were associated with poorer overall survival on multivariate Cox proportional hazard analysis (p<0.05). No specific HPV genotype affected survival.</p><p>Conclusion</p><p>Multiple HPV genotype infection was associated with poorer ICC survival in our study, compared with single genotype infection. HPV genotyping from FFPE tumor tissue using an automated assay such as the Onclarity BD™ assay provides a simpler alternative for routine clinical use.</p><p>Impact</p><p>This is the largest study employing an automated HPV genotyping assay using FFPE of ICC. Multiple HPV genotype infection adversely influenced survival.</p></div

Kaplan-Meier survival curves stratified by age (left panel), clinical stage (middle panel) and histological type (right panel).

<p>Kaplan-Meier survival curves stratified by age (left panel), clinical stage (middle panel) and histological type (right panel).</p

Multivariate predictors of overall survival according to Cox proportional hazard model.

<p>Multivariate predictors of overall survival according to Cox proportional hazard model.</p

Clinical and pathological parameters of all subjects with viable human DNA.

<p>Clinical and pathological parameters of all subjects with viable human DNA.</p

Distribution of the most frequent HPV genotypes according to clinical and pathological variables.

<p>Distribution of the most frequent HPV genotypes according to clinical and pathological variables.</p