RESUMO
OBJECTIVES: This study aimed to compare the interobserver Cohen κ on H&E staining and on H&E plus p16(INK4a) staining of all cervical biopsy specimens in a population-based screening program. METHODS: All the colposcopy-guided biopsies generated by the routine screening of 23,258 women aged 25 to 64 years were stained with H&E and H&E plus p16. Biopsy specimens were reviewed by six external experts. RESULTS: The four diagnoses were available in 441 cases. The interobserver κ values were 0.52 (95% confidence interval [CI], 0.45-0.58) and 0.48 (95% CI, 0.42-0.56) with H&E and H&E + p16, respectively, when using a five-group classification (normal, CIN 1, CIN 2, CIN 3, and cancer); adopting a two-group classification (≤CIN 1 and ≥CIN 2), the values were 0.75 (95% CI, 0.66-0.82) and 0.70 (95% CI, 0.61-0.79), respectively. CONCLUSIONS: The use of p16 on all cervical biopsy specimens in a screening program showed virtually no effect on reproducibility of the histologic diagnosis.
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 , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Displasia do Colo do Útero/metabolismo , Displasia do Colo do Útero/patologiaRESUMO
P16-INK4A overexpression has been proposed as a prognostic marker to manage the follow up of women with positive cytology and/or HPV test but without high-grade cervical intraepithelial neoplasia (CIN2+). This study measures the relative risk (RR) of CIN2+ of p16 positive versus negative in these women. All the women referred to colposcopy from October 2008 to September 2010 with negative or CIN1 colposcopy-guided biopsy were included in the study; women surgically treated or having a CIN2-3 were excluded. All baseline biopsies were dyed with hematoxylin and eosin and p16. Women were followed up according to screening protocols, with cytology or colposcopy at 6 or 12 months. CIN2/3 RRs and 95% confidence intervals (95%CI) were computed. Of 442 eligible women, 369 (83.5%) had at least one follow-up episode. At baseline, 113 (30.6%) were CIN1, 248 (67.2%) negative, and 8 (2.2%) inadequate histology; 293 (79.4%) were p16-negative, 64 (17.3%) p16 positive and 12 (3.2%) not valid. During follow up, we found ten CIN2 and three CIN3; of these, six were p16 positive (sensitivity 46%, 95% CI 19-75). The absolute risk among p16 positives was 9.4/100 compared to 1.7/100 of the p16 negatives (RR 5.5; 95% CI 1.7-17.4). The risk was also higher for CIN1 than for histologically negative women (RR 4.4; 95% CI 1.3-14.3). The RR for p16 in CIN1 did not change (RR 5.2; 95% CI 0.6-47.5). P16 overexpression is a good candidate for modulating follow-up intensity after a negative colposcopy but is limited by its low prospective sensitivity.
Assuntos
Biomarcadores Tumorais/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Infecções por Papillomavirus/patologia , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/virologia , Adulto , Carcinoma in Situ/epidemiologia , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patologia , Carcinoma in Situ/virologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Colposcopia , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/virologia , Prognóstico , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/virologia , Adulto Jovem , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/metabolismoRESUMO
The current anti-hepatitis C virus (HCV) therapy, based on pegylated-interferon alpha and ribavirin, has limited success rate and is accompanied by several side effects. The aim of this study was to identify protein profiles in pretreatment liver biopsies of HCV patients correlating with the outcome of antiviral therapy. Cytosolic or membrane/organelle-enriched protein extracts from liver biopsies of eight HCV patients were analyzed by two-dimensional fluorescence difference gel electrophoresis and mass spectrometry. Overall, this analysis identified 21 proteins whose expression levels correlate with therapy response. These factors are involved in interferon-mediated antiviral activity, stress response, and energy metabolism. Moreover, we found that post-translational modifications of dihydroxyacetone kinase were also associated with therapy outcome. Differential expression of the five best performing markers (STAT1, Mx1, DD4, DAK, and PD-ECGF) was confirmed by immunoblotting assays in an independent group of HCV patients. Finally, we showed that a prediction model based on the expression levels of these markers classifies responder and nonresponder patients with an accuracy of 85.7%. These results provide evidence that the analysis of pretreatment liver protein profiles is valuable for discriminating between responder and nonresponder HCV patients, and may contribute to reduce the number of nonresponder patients exposed to therapy-associated risks.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/metabolismo , Interferon-alfa/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Polietilenoglicóis/uso terapêutico , Proteoma/análise , Área Sob a Curva , Biomarcadores/análise , Biópsia , Análise por Conglomerados , Eletroforese em Gel Bidimensional , Hepatite C Crônica/diagnóstico , Humanos , Fígado/química , Análise de Componente Principal , Prognóstico , Proteômica , Proteínas Recombinantes/uso terapêutico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Ribavirina/uso terapêutico , Resultado do TratamentoRESUMO
Polypoid Spitz nevus represents a spitzoid melanocytic neoplasm that frequently has worrying and challenging histopathological details. Distinction from polypoid melanoma may not be straightforward. Two cases of polypoid Spitz nevus with striking histopathological features were studied. One case had prolonged follow up (Case 1) and one patient had undergone sentinel lymph node biopsy (Case 2), and fluorescence in situ hybridization (FISH) analysis was also completed (both cases). Follow up and genetic analysis of three control cases of polypoid melanoma is also presented. Our clinical and genetic results suggest that both the polypoid Spitz nevi were benign. The patients are alive with no evidence of disease. FISH analysis did not show abnormalities with probes tested. This is in sharp contrast with the control cases of polypoid melanoma, wherein genomic alterations were detectable. Our data indicate that the two polypoid lesions presented here are most probably benign, despite their worrying histopathological features. More cases with long-term follow up and greater numbers of DNA probes are necessary to extend this conclusion to other ambiguous melanocytic tumors.
Assuntos
DNA de Neoplasias/metabolismo , Nevo de Células Epitelioides e Fusiformes/metabolismo , Nevo de Células Epitelioides e Fusiformes/patologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Adulto , DNA de Neoplasias/genética , Seguimentos , Humanos , Hibridização in Situ Fluorescente/métodos , Masculino , Melanócitos/metabolismo , Melanócitos/patologia , Melanoma/genética , Melanoma/metabolismo , Melanoma/patologia , Pessoa de Meia-Idade , Nevo de Células Epitelioides e Fusiformes/genética , Sondas de Oligonucleotídeos/química , Sondas de Oligonucleotídeos/genética , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/genéticaAssuntos
Receptores ErbB/genética , Neoplasias Pulmonares/genética , Sarcoma/genética , Adulto , Idoso , Sequência de Bases , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , MutaçãoRESUMO
OBJECTIVE: To evaluate histomorphometric vascular characteristics from samples obtained by chorionic villus sampling (CVS) in pregnancies with low serum pregnancy-associated plasma protein-A (PAPP-A) levels and to relate these findings to three-dimensional (3D) placental volume and power Doppler vascularization. METHODS: Immediately before CVS, placental 3D-power Doppler ultrasonography was performed at 11 + 0 to 13 + 6 weeks in 12 pregnancies with PAPP-A concentrations <0.3 multiples of median (MoM) as well as in 11 control women. Using a standardized setting placental volume, vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were measured. Histomorphometric parameters of villi were blindly evaluated with a video-computerized-image-analysis system. RESULTS: Pregnancies with low PAPP-A showed a significantly reduced number of capillary vessels per villus cross-section (p = 0.005) and a smaller capillary diameter (p = 0.041). Placental vascular indices were significantly related to the number of fetal capillary vessels per villus (VI: r = 0.51, p = 0.03; FI: r = 0.48, p = 0.04; VFI: r = 0.56, p = 0.01). CONCLUSIONS: Differences in placental vascularization are present in first trimester in pregnancies with low PAPP-A and they are associated to altered 3D placental Doppler indices.
Assuntos
Vilosidades Coriônicas/anatomia & histologia , Placenta/irrigação sanguínea , Placenta/diagnóstico por imagem , Primeiro Trimestre da Gravidez/sangue , Proteína Plasmática A Associada à Gravidez/metabolismo , Ultrassonografia Pré-Natal/métodos , Vilosidades Coriônicas/diagnóstico por imagem , Vilosidades Coriônicas/ultraestrutura , Amostra da Vilosidade Coriônica , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Circulação Placentária/fisiologia , Gravidez , Primeiro Trimestre da Gravidez/metabolismo , Proteína Plasmática A Associada à Gravidez/análise , Ultrassonografia Doppler/métodosRESUMO
Endometrial cancer is the most common neoplasia of the female reproductive system, with the highest incidence among uterine malignancies, and is rarely associated with pregnancy. Thirty-five cases of pregnancy-associated endometrial cancer have been reported in literature, of which ours represents the 20th case diagnosed during the first trimester. A 39-year-old woman, gravida 4, para 2, was diagnosed with a focal, well- to moderately differentiated endometrial adenocarcinoma (International Federation of Gynecology and Obstetrics stage IA and grades G1 and G2) after dilatation and curettage (D&C) for a spontaneous abortion. The patient underwent progestational therapy and follow-up hysteroscopies and D&C to preserve fertility; she is alive and well 18 months after diagnosis. Recurrence of endometrial cancer coexisting with early pregnancy has not been reported in the literature. Conservative therapy for early endometrial cancer, diagnosed at the time of pregnancy, may be an option. Routine histologic examination after D&C performed for spontaneous abortion seems advisable.
Assuntos
Adenocarcinoma/diagnóstico , Neoplasias do Endométrio/diagnóstico , Complicações Neoplásicas na Gravidez/diagnóstico , Adulto , Feminino , Humanos , Achados Incidentais , Gravidez , Primeiro Trimestre da Gravidez , Fatores de TempoAssuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Leucemia Megacarioblástica Aguda/induzido quimicamente , Síndrome da Imunodeficiência Adquirida/complicações , Adulto , Biópsia , Crise Blástica , Medula Óssea/patologia , Humanos , Leucemia Megacarioblástica Aguda/patologia , MasculinoRESUMO
A new transperineal ultrasound-guided prostate rebiopsy method is described. The method is performed using a fixed grid approach similar to the method that has been in use for some time for brachytherapy i n prostate cancer. The method adopts special cylindrical cutting needles to take cores of varying lengths and was found to be more time consuming (this is the main reason it is mostly used for rebiopsies). It nevertheless allowed more accurate ard systematic mapping of the prostate gland than the standard method of taking multiple biopsies by sector. Sending in each biopsy fragment for separate histological examination based on grid coordinates allowed the Anatomical Pathology laboratory to build up an ideal topographic reconstruction of the disease lesions detected. The approach offers the advantages of a repeatable biopsy plan that can be compared with previous biopsies, more accurate spatial localisation of diseased tissue and accurate information on distribution within the gland. The benefits are multifold and all extremely interesting both for the diagnosis and subsequent choice, evaluation and administration of therapeutic treatment--and also for the dynamic study of evolving cell changes and cell structure anomalies detectable in the prostate gland.