RESUMO
Numerous chemical compounds are found in aquatic environments; among them are pesticides. Pesticides are widely used worldwide, and this use has progressively increased in recent decades, resulting in the accumulation of potentially toxic compounds in surface waters. Dimethylamine-based herbicides (DBH) and imidacloprid-based insecticides (IBI) have low soil absorption and high water solubility, facilitating the arrival of these compounds in aquatic environments. In this study, our objective was to analyze whether two pesticides, DBH and IBI at environmentally relevant concentrations of 320 µg/L for each compound, and their mixtures impact the behavioral and endocrine parameters of adult zebrafish, verifying the effect of pesticides on exploratory behavior and social and analyzing hormonal parameters related to stress. Acute exposure to the mixture of pesticides reduced fish locomotion. Pesticides alone and in combination did not affect cortisol levels in exposed animals. Pesticides, when tested together, can cause different effects on non-target organisms, and the evaluation of mixtures of these compounds is extremely important.
Assuntos
Locomoção , Neonicotinoides , Nitrocompostos , Praguicidas , Peixe-Zebra , Animais , Peixe-Zebra/fisiologia , Neonicotinoides/toxicidade , Locomoção/efeitos dos fármacos , Praguicidas/toxicidade , Nitrocompostos/toxicidade , Dimetilaminas , Poluentes Químicos da Água/toxicidadeRESUMO
ABSTRACT BACKGROUND: Managing cervical intraepithelial neoplasia grade 2 (CIN2) is challenging, considering the CIN2 regression rate, perinatal risks associated with excisional procedures, and insufficient well-established risk factors to predict progression. OBJECTIVES: To determine the ability of p16INK4a and Ki-67 staining in biopsies diagnosed with CIN2 to identify patients with higher-grade lesions (CIN3 or carcinoma). DESIGN AND SETTING: Cross-sectional study conducted at a referral center for treating uterine cervical lesions. METHODS: In 79 women, we analyzed the correlation of p16INK4a and Ki-67 expression in CIN2 biopsies with the presence of a higher-grade lesions, as determined via histopathology in surgical specimens from treated women or via two colposcopies and two cytological tests during follow-up for untreated women with at least a 6-month interval. The expression of these two biomarkers was verified by at least two independent pathologists and quantified using digital algorithms. RESULTS: Thirteen (16.8%) women with CIN2 biopsy exhibited higher-grade lesions on the surgical excision specimen or during follow-up. p16INK4a expression positively and negatively predicted the presence of higher-grade lesions in 17.19% and 86.67% patients, respectively. Ki-67 expression positively and negatively predicted the presence of higher-grade lesions in 40% and 88.24% patients, respectively. CONCLUSIONS: Negative p16INK4a and Ki67 immunohistochemical staining can assure absence of a higher-grade lesion in more than 85% of patients with CIN2 biopsies and can be used to prevent overtreatment of these patients. Positive IHC staining for p16INK4a and Ki-67 did not predict CIN3 in patients with CIN2 biopsies.
RESUMO
We describe a strategy for the development of a rational approach of neoplastic disease therapy based on the demonstration that scale-free networks are susceptible to specific attacks directed against its connective hubs. This strategy involves the (i) selection of up-regulated hubs of connectivity in the tumors interactome, (ii) drug repurposing of these hubs, (iii) RNA silencing of non-druggable hubs, (iv) in vitro hub validation, (v) tumor-on-a-chip, (vi) in vivo validation, and (vii) clinical trial. Hubs are protein targets that are assessed as targets for rational therapy of cancer in the context of personalized oncology. We confirmed the existence of a negative correlation between malignant cell aggressivity and the target number needed for specific drugs or RNA interference (RNAi) to maximize the benefit to the patient's overall survival. Interestingly, we found that some additional proteins not generally targeted by drug treatments might justify the addition of inhibitors designed against them in order to improve therapeutic outcomes. However, many proteins are not druggable, or the available pharmacopeia for these targets is limited, which justifies a therapy based on encapsulated RNAi.
Assuntos
Neoplasias , Mapeamento de Interação de Proteínas , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genéticaRESUMO
Early stages of cervical cancer in young women need conservative treatments. Electrosurgical therapies (LLETZ, LEEP, SWETZ, NETZ) have been recommended for these women. However, there are recommendations to perform a second excision when the specimen margins are not free of disease. This can lead to some important complications. This article aims to verify the frequency of residual invasive or microinvasive disease after the excisional procedure in women with IA1CC. Data on women with IA1CC diagnosed between 1990 and 2022, were retrieved from medical records. Post-treatment disease was detected during a second surgical procedure or postoperative follow-up. Among the 69 included women, three (4.3 percent; CI95 percent 0-9.2) had residual microinvasive lesions, while none showed invasive disease during a second procedure or follow-up. Only the age of 37 years or more was significantly related to the presence of preinvasive or microinvasive residual lesions. Nearly 80 percent of the women who underwent a second procedure showed no residual lesions. The absence of invasive disease in a second procedure or during the follow-up of these women and the large proportion of women with no residual lesion questions the need for a new surgical procedure even when the surgical margins of the initial specimen are involved.
Assuntos
Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Feminino , Humanos , Adulto , Neoplasias do Colo do Útero/cirurgia , Conização/métodos , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Histerectomia , Estudos RetrospectivosRESUMO
BACKGROUND: Managing cervical intraepithelial neoplasia grade 2 (CIN2) is challenging, considering the CIN2 regression rate, perinatal risks associated with excisional procedures, and insufficient well-established risk factors to predict progression. OBJECTIVES: To determine the ability of p16INK4a and Ki-67 staining in biopsies diagnosed with CIN2 to identify patients with higher-grade lesions (CIN3 or carcinoma). DESIGN AND SETTING: Cross-sectional study conducted at a referral center for treating uterine cervical lesions. METHODS: In 79 women, we analyzed the correlation of p16INK4a and Ki-67 expression in CIN2 biopsies with the presence of a higher-grade lesions, as determined via histopathology in surgical specimens from treated women or via two colposcopies and two cytological tests during follow-up for untreated women with at least a 6-month interval. The expression of these two biomarkers was verified by at least two independent pathologists and quantified using digital algorithms. RESULTS: Thirteen (16.8%) women with CIN2 biopsy exhibited higher-grade lesions on the surgical excision specimen or during follow-up. p16INK4a expression positively and negatively predicted the presence of higher-grade lesions in 17.19% and 86.67% patients, respectively. Ki-67 expression positively and negatively predicted the presence of higher-grade lesions in 40% and 88.24% patients, respectively. CONCLUSIONS: Negative p16INK4a and Ki67 immunohistochemical staining can assure absence of a higher-grade lesion in more than 85% of patients with CIN2 biopsies and can be used to prevent overtreatment of these patients. Positive IHC staining for p16INK4a and Ki-67 did not predict CIN3 in patients with CIN2 biopsies.
Assuntos
Carcinoma , Displasia do Colo do Útero , Gravidez , Humanos , Feminino , Masculino , Antígeno Ki-67 , Estudos Transversais , BiópsiaRESUMO
BACKGROUND: According to the Brazilian Guidelines on Cervical Cancer Screening, women with cytopathologic diagnosis of high-grade intraepithelial lesion, abnormal colposcopic findings, fully visible squamocolumnar junction and age 25 years or older should be treated at the first visit ("see and treat-S&T"). The main limitation to this approach is the risk of overtreatment, identified by histology without preinvasive lesion. The objectives of this study were to identify the overtreatment rate in women undergoing S&T in cervical cancer prevention at a referral center with extensive experience with the method and to detect possible factors associated with this rate. METHODS: This was a cross-sectional study that analyzed records from a database with 616 women submitted to S&T from 1996 to 2017. Negative histology was defined as the following histopathologic results: human papillomavirus without cervical intraepithelial neoplasia (CIN), inflammatory, low-grade squamous intraepithelial lesion, and CIN 1. RESULTS: Of the 616 women, there were 52 (8.44%, 95%CI 6.25-10.64%) with a histopathologic report without preinvasive cervical lesion. No statistical association was found between this outcome and age or a significant downward trend over time. CONCLUSION: The overtreatment rate in this study can be considered low and consistent with the acceptable rates reported in the literature, reinforcing the prevailing Brazilian guideline, in which the benefits of immediate treatment outweigh the risk of losses following biopsy.
Assuntos
Colposcopia , Neoplasias do Colo do Útero , Adulto , Brasil/epidemiologia , Colposcopia/métodos , Estudos Transversais , Detecção Precoce de Câncer , Feminino , Humanos , Gravidez , Encaminhamento e Consulta , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia , Esfregaço VaginalRESUMO
BACKGROUND: Cervical cancer screening in Brazil is done using Pap smears. Women who are most likely to have a preinvasive lesion or cervical cancer are immediately referred for colposcopy. OBJECTIVE: The aim of this study was to evaluate the diagnostic performance of endocervical cytological tests in diagnosing preinvasive cervical lesions in women with initial high-grade squamous intraepithelial lesions (HSIL), or atypical squamous cells in which high-grade lesions could not be ruled out (ASC-H), or atypical glandular cells (AGC), and whose colposcopy did not show any abnormalities, with no fully visible transformation zone (types 2 and 3). DESIGN AND SETTING: Retrospective observational study conducted in Rio de Janeiro, Brazil. METHODS: Data from women who came to the cervical pathology outpatient clinic between January 2012 and April 2017 were analyzed. The results from endocervical cytological tests were compared with the final diagnosis, which was obtained through examination of a surgical specimen or, among women who did not undergo an excisional procedure, after cytological and colposcopic follow-up for two years. RESULTS: We included 78 women. The sensitivity of endocervical cytological tests was 72.7%; specificity 98.5%; positive and negative predictive values 88.9% and 95.6%, respectively; and positive and negative likelihood ratios 48.7 and 0.28. CONCLUSION: Endocervical cytological tests are simple, inexpensive and noninvasive, and form a reliable method for determining management among patients with HSIL, ASC-H and AGC cytological findings and negative colposcopic findings without visualization of the squamocolumnar junction.
Assuntos
Displasia do Colo do Útero , Neoplasias do Colo do Útero , Brasil , Colposcopia , Detecção Precoce de Câncer , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Esfregaço VaginalRESUMO
ABSTRACT BACKGROUND: Cervical cancer screening in Brazil is done using Pap smears. Women who are most likely to have a preinvasive lesion or cervical cancer are immediately referred for colposcopy. OBJECTIVE: The aim of this study was to evaluate the diagnostic performance of endocervical cytological tests in diagnosing preinvasive cervical lesions in women with initial high-grade squamous intraepithelial lesions (HSIL), or atypical squamous cells in which high-grade lesions could not be ruled out (ASC-H), or atypical glandular cells (AGC), and whose colposcopy did not show any abnormalities, with no fully visible transformation zone (types 2 and 3). DESIGN AND SETTING: Retrospective observational study conducted in Rio de Janeiro, Brazil. METHODS: Data from women who came to the cervical pathology outpatient clinic between January 2012 and April 2017 were analyzed. The results from endocervical cytological tests were compared with the final diagnosis, which was obtained through examination of a surgical specimen or, among women who did not undergo an excisional procedure, after cytological and colposcopic follow-up for two years. RESULTS: We included 78 women. The sensitivity of endocervical cytological tests was 72.7%; specificity 98.5%; positive and negative predictive values 88.9% and 95.6%, respectively; and positive and negative likelihood ratios 48.7 and 0.28. CONCLUSION: Endocervical cytological tests are simple, inexpensive and noninvasive, and form a reliable method for determining management among patients with HSIL, ASC-H and AGC cytological findings and negative colposcopic findings without visualization of the squamocolumnar junction.
Assuntos
Humanos , Feminino , Gravidez , Neoplasias do Colo do Útero , Displasia do Colo do Útero , Esfregaço Vaginal , Brasil , Estudos Retrospectivos , Colposcopia , Detecção Precoce de CâncerRESUMO
Importin-ß, exportin-5, p16, Ki-67, Mcl1, PDL1, and cFLIP are each over-expressed in the majority of CIN 1 lesions. These biomarkers, plus HPV E6/E7 RNA, were analyzed in carcinoma-in-situ (CIS), microinvasive, and squamous cell carcinoma (SCC) of the uterine cervix and cervical carcinoma cell lines. Only p16 and Ki-67 continued to be over-expressed in CIS, with a concomitant marked increase in E6/E7 RNA. There was a highly significant increase in PDL1 expression and decrease in Ki-67 (each pâ¯<â¯0.001) in microinvasive cancer compared to CIS whereas p16 and E6/E7 remained stable. As the lesion progressed to SCC, p16 and E6/E7 RNA remained strongly overexpressed with a concomitant over expression of importin-ß and Ki67. HPV positive Caski cells showed significant elevations of p16, importin-ß, exportin-5 and PDL1 compared to the HPV negative cervical cancer cell line C33A, consistent with viral induction of these biomarkers. The data suggest that PDL1 may be a useful biomarker to differentiate CIS from microinvasive cancer and, thus, anti-PDL1 therapy may inhibit the progression of CIS to the invasive stage.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/patologia , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Antígeno B7-H1/biossíntese , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Protein p16 has been extensively studied as a potential biomarker for precursor lesions to distinguish cervical Intraepithelial neoplasia (CIN) from their mimics. However, the use of p16 as prognostic biomarker for diagnosis of cervical cancer and precancer is controversial. This study focuses on the assessment of peer-reviewed scientific data related to the use of p16 to predict disease severity and its controversies. METHODS: We reviewed publications in MEDLINE/PubMed assessing the clinical, diagnostic and prognostic significance of p16 in CIN and cervical cancer; we included publications from 2009 to June 2017. RESULTS: The use of p16 as a prognostic marker is still unreliable, although it could be a useful tool for diagnosis of Cervical Intraepithelial Neoplasia lesions with undetermined morphology. Moreover, p16 appears to be a specific marker of high-risk oncogenic HPV infection. CONCLUSION: This review shows the potential utility and drawbacks of p16 for clinical practice and the diagnosis of cervical cancer. Further studies are required to substantiate the role of p16 in conjunction with other more sensitive and specific biomarkers for diagnosing CIN and predicting its progression.
INTRODUÇÃO: A proteína p16 tem sido estudada como um biomarcador potencialmente específico de lesões cervicais precursoras e como uma forma de diferenciar as lesões parecidas com Neoplasia intra-epitelial cervical (NIC). Contudo existem várias controvérsias sobre a utilização de p16 como um biomarcador prognóstico e como uma ferramenta para o diagnóstico de câncer cervical e de lesões pré-câncer. O objetivo deste estudo foi a revisão de dados científicos por pares de bases, relacionados com a utilização da p16 e suas controvérsias. MÉTODOS: O estudo foi projetado como uma revisão da literatura das publicações do Medline/PubMed que avaliam o significado clínico, diagnóstico ou prognóstico do p16 em lesões de NIC e no câncer cervical no período de janeiro de 2009 a junho de 2017. RESULTADOS: o uso do p16 como um marcador prognóstico ainda não é confiável, apesar de que a p16 poderia ser uma ferramenta útil para o diagnóstico em lesões de NIC com morfologia indeterminada. Além disso, a p16 parece ser um marcador específico de infecção por HPV de alto risco oncogênico. CONCLUSÃO: A presente revisão mostra a potencial utilidade da proteína p16, bem como os inconvenientes para uso clínico-patológico e diagnóstico no câncer cervical. Contudo são necessários mais estudos para fundamentar o papel da p16 em conjunto com os outros biomarcadores mais sensíveis e específicos para diagnosticar NIC e prever a sua progressão.
Assuntos
Humanos , Biomarcadores Tumorais , Neoplasias do Colo do Útero/diagnóstico , Displasia do Colo do Útero , Infecções por PapillomavirusRESUMO
A major concern associated with ZIKV infection is the increased incidence of microcephaly with frequent calcifications in infants born from infected mothers. To date, postmortem analysis of the central nervous system (CNS) in congenital infection is limited to individual reports or small series. We report a comprehensive neuropathological study in ten newborn babies infected with ZIKV during pregnancy, including the spinal cords and dorsal root ganglia (DRG), and also muscle, pituitaries, eye, systemic organs, and placentas. Using in situ hybridization (ISH) and electron microscopy, we investigated the role of direct viral infection in the pathogenesis of the lesions. Nine women had Zika symptoms between the 4th and 18th and one in the 28th gestational week. Two babies were born at 32, one at 34 and 36 weeks each and six at term. The cephalic perimeter was reduced in four, and normal or enlarged in six patients, although the brain weights were lower than expected. All had arthrogryposis, except the patient infected at 28 weeks gestation. We defined three patterns of CNS lesions, with different patterns of destructive, calcification, hypoplasia, and migration disturbances. Ventriculomegaly was severe in the first pattern due to midbrain damage with aqueduct stenosis/distortion. The second pattern had small brains and mild/moderate (ex-vacuo) ventriculomegaly. The third pattern, a well-formed brain with mild calcification, coincided with late infection. The absence of descending fibres resulted in hypoplastic basis pontis, pyramids, and cortico-spinal tracts. Spinal motor cell loss explained the intrauterine akinesia, arthrogryposis, and neurogenic muscle atrophy. DRG, dorsal nerve roots, and columns were normal. Lympho-histiocytic inflammation was mild. ISH showed meningeal, germinal matrix, and neocortical infection, consistent with neural progenitors death leading to proliferation and migration disorders. A secondary ischemic process may explain the destructive lesions. In conclusion, we characterized the destructive and malformative consequences of ZIKV in the nervous system, as reflected in the topography and severity of lesions, anatomic localization of the virus, and timing of infection during gestation. Our findings indicate a developmental vulnerability of the immature CNS, and shed light on possible mechanisms of brain injury of this newly recognized public health threat.
Assuntos
Encéfalo/patologia , Microcefalia/patologia , Complicações Infecciosas na Gravidez , Medula Espinal/patologia , Infecção por Zika virus/congênito , Infecção por Zika virus/patologia , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Olho/diagnóstico por imagem , Olho/patologia , Feminino , Humanos , Recém-Nascido , Masculino , Microcefalia/diagnóstico por imagem , Microcefalia/etiologia , Músculo Esquelético/patologia , Hipófise/diagnóstico por imagem , Hipófise/patologia , Gravidez , Medula Espinal/diagnóstico por imagem , Adulto Jovem , Infecção por Zika virus/complicações , Infecção por Zika virus/diagnóstico por imagemRESUMO
OBJECTIVE: The aim of this study was to evaluate secretory leukocyte protease inhibitor (SLPI) expression in anal biopsies from HIV-positive (HIV+) individuals, and compare that to anal intraepithelial neoplasia (AIN) diagnoses and human papillomavirus (HPV) status. DESIGN: This is a cross-sectional study of a cohort of 54 HIV+ (31 males and 23 females) from an AIDS clinic in Rio de Janeiro, Brazil. METHODS: The study material consisted of anorectal tissue biopsies obtained from HIV+ subjects, which were used to construct tissue microarray paraffin blocks for immunohistochemical analysis of SLPI expression. Biopsies were evaluated by an expert pathologist and classified as low-grade AIN1, high-grade AIN2/3, or normal squamous epithelium. In addition, DNA from the biopsies was extracted and analyzed for the presence of low- or high-risk HPV DNA. RESULTS: Histologically, normal squamous epithelium from the anorectal region showed strong positive SLPI staining in 17/20 (85%) samples. In comparison, 9/17 (53%) dysplastic squamous epithelial samples from AIN1 patients showed strong SLPI staining, and only 5/17 (29%) samples from AIN2/3 patients exhibited strong SPLI staining, which both were significantly fewer than those from normal tissue (P = 0.005). Furthermore, there was a significantly higher proportion of samples in which oncogenic high-risk HPV genotypes were detected in low SLPI-expressing tissues than that in tissues with high SLPI expression (P = 0.040). CONCLUSIONS: Taken together these results suggest that low SLPI expression is associated with high-risk HPV infections in the development of AIN.
Assuntos
Alphapapillomavirus/isolamento & purificação , Doenças do Ânus/complicações , Infecções por HIV/complicações , Inibidor Secretado de Peptidases Leucocitárias/metabolismo , Adulto , Doenças do Ânus/metabolismo , Doenças do Ânus/patologia , Doenças do Ânus/virologia , Biópsia , Brasil , Feminino , Infecções por HIV/metabolismo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The discovery of the human papillomavirus (HPV) vaccine illustrates the power of in situ-based pathologic analysis in better understanding and curing diseases. The 2 available HPV vaccines have markedly reduced the incidence of cervical intraepithelial neoplasias, genital warts, and cervical cancer throughout the world. Concerns about HPV vaccine safety have led some physicians, health care officials, and parents to refuse providing the recommended vaccination to the target population. The aims of the study were to discuss the discovery of HPV vaccine and review scientific data related to measurable outcomes from the use of HPV vaccines. The strong type-specific immunity against HPV in humans has been known for more than 25 years. Multiple studies confirm the positive risk benefit of HPV vaccination with minimal documented adverse effects. The most common adverse effect, injection site pain, occurred in about 10% of girls and was less than the rate reported for other vaccines. Use of HPV vaccine should be expanded into more diverse populations, mainly in low-resource settings.
Assuntos
Condiloma Acuminado/prevenção & controle , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Displasia do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Vacinação/efeitos adversos , Condiloma Acuminado/virologia , Feminino , Humanos , Masculino , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/efeitos adversos , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/virologiaRESUMO
Acroangiodermatitis is an angioproliferative disease usually related to chronic venous insufficiency, and it is considered a clinical and histological simulator of Kaposi's sarcoma (KS). Immunohistochemistry is the suitable method to differentiate between these two entities. It reveals the following immunostaining profile: immunopositivity with anti-CD34 antibody is restricted to the vascular endothelium in acroangiodermatitis, and diffuse in the KS (endothelial cells and perivascular spindle cells); immunopositivity with anti-HHV-8 only in KS cases. We report the case of an HIV seropositive patient without apparent vascular disease, who presented violaceous and brownish erythematous lesions on the feet, and whose histopathology and immunohistochemistry indicated the diagnosis of acroangiodermatitis.
Assuntos
Acrodermatite/patologia , Soropositividade para HIV/patologia , Hepatite C/patologia , Sarcoma de Kaposi/patologia , Sífilis/patologia , Acrodermatite/tratamento farmacológico , Adulto , Coinfecção/patologia , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Masculino , Pele/patologiaRESUMO
Acroangiodermatitis is an angioproliferative disease usually related to chronic venous insufficiency, and it is considered a clinical and histological simulator of Kaposi's sarcoma (KS). Immunohistochemistry is the suitable method to differentiate between these two entities. It reveals the following immunostaining profile: immunopositivity with anti-CD34 antibody is restricted to the vascular endothelium in acroangiodermatitis, and diffuse in the KS (endothelial cells and perivascular spindle cells); immunopositivity with anti-HHV-8 only in KS cases. We report the case of an HIV seropositive patient without apparent vascular disease, who presented violaceous and brownish erythematous lesions on the feet, and whose histopathology and immunohistochemistry indicated the diagnosis of acroangiodermatitis.
Assuntos
Adulto , Humanos , Masculino , Acrodermatite/patologia , Soropositividade para HIV/patologia , Hepatite C/patologia , Sarcoma de Kaposi/patologia , Sífilis/patologia , Acrodermatite/tratamento farmacológico , Coinfecção/patologia , Diagnóstico Diferencial , Imuno-Histoquímica , Pele/patologiaRESUMO
UNLABELLED: Cell cycle protein expression plays an important role in the pathophysiology of cervical cancer. However, few studies have attempted to correlate the use of these biomarkers with the clinical progression of the tumor. OBJECTIVES: 1) To analyze the expression of Ki-67, p53 and p16(INK4a) in cervical cancer, 2) to correlate the relative expression of these proteins as well as clinical parameters with the stage of disease, and 3) to determine the HPV DNA prevalence and subtype distribution. METHODS: Tissue Micro-Arrays (TMA) from patients with invasive cervical cancer (ICC) and controls were analyzed. HPV DNA detection was done by PCR and in situ hybridization. Ki-67, p53 and p16(INK4a) were analyzed by immunohistochemistry; clinical data was derived from the chart review. RESULTS: Advanced tumor stage (III and IV) was strongly associated (p<0.005) with advanced age (>55 years old), with more than four pregnancies and with the lack of formal education. HPV DNA was found in 94.3% of cases with the most prevalent types being HPV16 (67.5%), followed by HPV33 (12.0%) and HPV35 (3.6%). High expression of Ki-67 and p16 was more common in the advanced FIGO stages (pâ=â0.023). Women with HPV16 tended to be younger (50.9 years; SE 1.9) compared to women with other types (59.9 years; SE 2.8). CONCLUSION: We found that Ki-67 and p16 expression were independently associated with the tumor stage. We also noted that about 1/3 of the cervical cancers in this Brazilian cohort were not associated with HPV types directly targeted by the current HPV vaccines.
Assuntos
Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Biomarcadores Tumorais , Brasil/epidemiologia , Estudos de Casos e Controles , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Estudos de Coortes , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Progressão da Doença , Feminino , Genótipo , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Prevalência , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia , Adulto JovemRESUMO
Este trabalho avalia o conhecimento e a opinião de pacientes ambulatoriais de um hospital-escola a respeito da participação de acadêmicos de Medicina nos atendimentos. Aplicaram-se questionários com perguntas objetivas e dissertativas a 131 pacientes enquanto aguardavam primeira consulta médica na unidade. Dos entrevistados, 58,8% sabiam o que significava o termo "hospital-escola" e 57,3% tinham conhecimento de que o hospital analisado se inclui nesse conceito. Apenas 6,9% dos pacientes afirmaram ter recebido explicações sobre o conceito e funcionamento do hospital-escola no momento da marcação da consulta e 36,6% relataram não saber que seriam atendidos por estudantes supervisionados pelo médico professor. Quanto à opinião sobre o atendimento por alunos, 69,5% o consideram bom e importante para o aprendizado deles, que serão os médicos do futuro; 26,7% não se incomodam; e 3,1% preferem atendimento exclusivo pelo médico. Após análise, verificou-se que mais de um terço dos pacientes não sabia que seria atendido por estudantes e que há necessidade de informá-los sobre a dinâmica de atendimento médico no momento do agendamento das consultas.
The goal of this paper is to evaluate the knowledge and opinions of patients in a university hospital on the participation of medical students in medical appointments. Questionnaires with "yes" or "no" closed questions and open questions were answered by 131 patients while they were waiting for their first medical appointment at the hospital. 58.8% of respondents knew the meaning of "teaching hospital" and 57.3% knew that the hospital fell within this category. Only 6.9% of patients reported having received information on the definition and particularities of a teaching hospital when scheduling their appointments, and 36.6% reported not knowing that they would be attended by students supervised by a physician teacher. 69.5% of patients considered being attended by a student positively, as an important step in the students' learning process; 26.7% did not mind being attended to by a medical student, and 3.1% would have preferred to have been attended to by a qualified physician only. This study has concluded that it is necessary to inform patients of the particularities of teaching hospitals when they schedule their appointments.
RESUMO
Although several studies have evaluated the role of p16(INK4a) as a diagnostic marker of cervical intraepithelial neoplasia (CIN) and its association with disease progression, studies regarding the role of p16(INK4a) in human immunodeficiency virus (HIV)-infected patients remain scarce. The present study was designed to determine the potential utility of p16(INK4a) as a diagnostic marker for CIN and invasive cervical cancer in HIV-positive and negative cervical specimens. An immunohistochemical analysis of p16(INK4a) was performed in 326 cervical tissue microarray specimens. Performance indicators were calculated and compared using receiving operating characteristics curve (ROC)/area under the curve. In HIV-1-negative women, the percentage of cells that was positive for p16(INK4a) expression was significantly correlated with the severity of CIN (p < 0.0001). A ROC curve with a cut-off value of 55.28% resulted in a sensitivity of 89%, a specificity of 81%, a positive predictive value of 91% and a negative predictive value of 78%. HIV-seropositive women exhibited decreased expression of p16(INK4a) in CIN2-3 specimens compared with HIV-negative specimens (p = 0.031). The ROC data underscore the potential utility of p16(INK4a) under defined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. HIV-1 infection, however, is associated with relatively reduced p16(INK4a) expression in CIN 2-3.
Assuntos
Biomarcadores Tumorais/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Estudos de Casos e Controles , Feminino , Infecções por HIV/complicações , HIV-1 , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Curva ROC , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/metabolismo , Displasia do Colo do Útero/complicações , Displasia do Colo do Útero/metabolismoRESUMO
Although several studies have evaluated the role of p16INK4a as a diagnostic marker of cervical intraepithelial neoplasia (CIN) and its association with disease progression, studies regarding the role of p16INK4a in human immunodeficiency virus (HIV)-infected patients remain scarce. The present study was designed to determine the potential utility of p16INK4a as a diagnostic marker for CIN and invasive cervical cancer in HIV-positive and negative cervical specimens. An immunohistochemical analysis of p16INK4a was performed in 326 cervical tissue microarray specimens. Performance indicators were calculated and compared using receiving operating characteristics curve (ROC)/area under the curve. In HIV-1-negative women, the percentage of cells that was positive for p16INK4a expression was significantly correlated with the severity of CIN (p < 0.0001). A ROC curve with a cut-off value of 55.28% resulted in a sensitivity of 89%, a specificity of 81%, a positive predictive value of 91% and a negative predictive value of 78%. HIV-seropositive women exhibited decreased expression of p16INK4a in CIN2-3 specimens compared with HIV-negative specimens (p = 0.031). The ROC data underscore the potential utility of p16INK4a under defined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. HIV-1 infection, however, is associated with relatively reduced p16INK4a expression in CIN 2-3.