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1.
PLoS One ; 7(10): e47007, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23056557

RESUMO

BACKGROUND: Nonlinear optical (NLO) microscopy techniques have potential to improve the early detection of epithelial ovarian cancer. In this study we showed that multimodal NLO microscopies, including two-photon excitation fluorescence (TPEF), second-harmonic generation (SHG), third-harmonic generation (THG) and fluorescence lifetime imaging microscopy (FLIM) can detect morphological and metabolic changes associated with ovarian cancer progression. METHODOLOGY/PRINCIPAL FINDINGS: We obtained strong TPEF + SHG + THG signals from fixed samples stained with Hematoxylin & Eosin (H&E) and robust FLIM signal from fixed unstained samples. Particularly, we imaged 34 ovarian biopsies from different patients (median age, 49 years) including 5 normal ovarian tissue, 18 serous tumors and 11 mucinous tumors with the multimodal NLO platform developed in our laboratory. We have been able to distinguish adenomas, borderline, and adenocarcinomas specimens. Using a complete set of scoring methods we found significant differences in the content, distribution and organization of collagen fibrils in the stroma as well as in the morphology and fluorescence lifetime from epithelial ovarian cells. CONCLUSIONS/SIGNIFICANCE: NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns for serous and mucinous ovarian tumors. The results provide a basis to interpret future NLO images of ovarian tissue and lay the foundation for future in vivo optical evaluation of premature ovarian lesions.


Assuntos
Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/patologia , Microscopia , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Soro/metabolismo , Adenocarcinoma Mucinoso/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Epitelial do Ovário , Feminino , Humanos , Microscopia de Fluorescência por Excitação Multifotônica , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/metabolismo , Ovário/metabolismo , Ovário/patologia
2.
Scand J Immunol ; 74(3): 244-252, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21595734

RESUMO

Methods for ex vivo expansion of natural killer (NK) cells have allowed obtaining enough numbers of human NK cells for clinical trials. However, the evaluation of these methods has been mostly limited to haematological malignancies. This study aimed at evaluating a method for selective expansion of NK cells when applied in peripheral blood mononuclear cells (PBMC) of patients with ovarian neoplasia. PBMC from 13 volunteer patients with ovarian neoplasia, seven benign and six malignant tumours, were cultured in CellGro medium supplemented with anti-CD3 (9-10 initial days), IL-2 and foetal bovine serum for 21 days. The resulting effector cells were evaluated for their phenotype, cytotoxicity and cytokine secretion. PBMC cultures resulted in multiple populations (NK, NKT and T) of effector cells, enriched with CD56(+) lymphocytes. NK cells from patients with benign and malignant ovarian neoplasia were expanded 139.6 ± 63.4 and 82.7 ± 25.3-fold, respectively, being the largest lymphocyte subtype among CD56(+) population. Effector cells expanded from patients with malignant ovarian neoplasia had higher proportion of T lymphocytes and altered cytokine production patterns, characterized by lower INF-γ, TNF-α and higher IL-4, compared with patients with benign ovarian neoplasia. Effector cells were cytotoxic against K562 and OVCAR3 cell lines. Cytotoxicity was significantly higher (P < 0.05) using magnetically separated CD56(+) effector cell fractions compared with CD56-deprived ones. The present study demonstrates the feasibility of the culture system employed to generate effector cells, enriched with CD56(+) lymphocytes, from PBMC of patients with ovarian neoplasia. NK cells were the largest lymphocyte subtype among the CD56(+) population and the main variable among the final effector cell preparation affecting target cell killing.


Assuntos
Células Matadoras Naturais/imunologia , Leucócitos Mononucleares/imunologia , Células T Matadoras Naturais/imunologia , Neoplasias Ovarianas/imunologia , Adulto , Anticorpos Monoclonais , Complexo CD3/imunologia , Antígeno CD56/análise , Células Cultivadas , Citocinas/biossíntese , Citotoxicidade Imunológica , Feminino , Citometria de Fluxo , Humanos , Contagem de Linfócitos , Pessoa de Meia-Idade
4.
Cytopathology ; 19(1): 34-43, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18205627

RESUMO

OBJECTIVE: To analyse the correlation between cytomorphological criteria in smears with atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) and human papillomavirus (HPV) reflex test results with different neoplastic histological diagnoses, particularly to distinguish between glandular and squamous neoplasia. METHODS: A series of 155 women with glandular abnormalities in their conventional cervical smears was included: 106 with AGC, 35 with AGC associated with high-grade squamous intraepithelial lesion (HSIL) and 14 with AIS. Two reviewers evaluated 35 cytomorphological criteria and hybrid capture II (HCII) was performed in all cases. Colposcopy was carried out in all cases and biopsy in 126/155. For statistical purposes, predictive values and odds ratio (OR) were calculated, followed by chi-square automatic interaction detection. RESULTS: Histology detected 56 cases of squamous and 17 of glandular intraepithelial or invasive neoplasia. Predictive values of the papillary groups and feathering criteria for glandular neoplasia were, respectively, 80.0% and 73.3%. Feathering was the criterion with the highest OR for distinguishing glandular from squamous neoplasia and also for distinguishing between glandular and non-neoplastic diagnosis. Rosettes and pseudostratified strips did not perform as well. Multivariant Classification and Regression Trees analysis identified feathering as the best criterion for distinguishing between glandular, squamous and non-neoplastic diagnoses regardless of HPV status. CONCLUSIONS: Feathering was the best criterion for predicting glandular neoplasia.


Assuntos
Adenocarcinoma/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Infecções por Papillomavirus/complicações , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adenocarcinoma/virologia , Carcinoma de Células Escamosas/virologia , Feminino , Humanos , Papillomaviridae , Valor Preditivo dos Testes , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Displasia do Colo do Útero/virologia
5.
Int J Gynecol Cancer ; 17(3): 607-14, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17504375

RESUMO

The objective of this study was to assess the expression of Cyclooxygenase-2 (COX-2) and cell proliferation activity (Ki67 expression) in benign, borderline, and malignant serous and mucinous ovarian tumors. Expression of COX-2 and Ki67 proteins were evaluated by immunohistochemistry, in paraffin-embedded sections of ovarian epithelial tumors. The study included 113 serous (67 benign, 15 borderline, and 31 malignant) and 85 mucinous (48 benign, 28 borderline, and 9 malignant) tumors, removed from women who underwent laparotomy between January 1997 and December 2003. From benign to malignant tumors, there was a progressive positive trend in COX-2 expression in both serous and mucinous tumors, more evident in mucinous ones (P < 0.001). Comparing histologic types, COX-2 expression was more prominent in serous than in mucinous benign tumors (P < 0.01), but this difference was not significant in the borderline (P= 0.11) or malignant categories (P= 0.71). There was a progressive Ki67 positivity in line with the tumor histologic gradient for both serous (P < 0.01) and mucinous lesions (P < 0.01), but this increasing expression did not correlate with COX-2 expression in the present series (P= 0.78). There was a higher COX-2 expression in serous ovarian adenomas than in mucinous ones. COX-2 positivity increases in line with the morphologic gradient, from benign to malignant in both histologic types, but it was more prominent in mucinous lesions, pointing to different oncogenic pathways related to different histologic types. A correlation between the expression of COX-2 and Ki67 was not found, suggesting that COX-2 may be required for carcinogenesis, but this pathway is not responsible for cell proliferation in ovarian tumors.


Assuntos
Adenocarcinoma Mucinoso/metabolismo , Proliferação de Células , Ciclo-Oxigenase 2/metabolismo , Cistadenocarcinoma Seroso/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias Ovarianas/metabolismo , Adenocarcinoma Mucinoso/patologia , Adulto , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia
6.
Int J Gynecol Cancer ; 16(3): 1055-62, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16803485

RESUMO

The objective of this study was to assess whether human papillomavirus (HPV) detection with hybrid capture II (HC II) can help predict the presence and the nature, glandular or squamous, of histologic cervical lesions in women referred due to atypical glandular cells (AGC) or high-grade squamous intraepithelial lesion (HSIL). A total of 247 women were included. Referral Pap smears comprised AGC (51 cases), AGC plus HSIL (28 cases), adenocarcinoma in situ (10 cases), and HSIL (158 cases). All patients were tested for high-risk HPV with HC II and had a histologic assessment of their cervix. Histologic analysis showed 38 women with (15.3%) cervicitis, 194 with (75.5%) squamous lesions, and 15 with (9.2%) glandular neoplasia. The overall rate of high-risk HPV detection was 77%. Almost 70% of AGC-HPV-negative patients did not have a pathologically proven cervical neoplasia, whereas 76% of women with AGC-HPV-positive result were diagnosed with a squamous or glandular neoplasia. Most (95%) of the lesions in patients with AGC-HSIL were of squamous nature, and HPV detection did not contribute to their differentiation from glandular lesions. We conclude that in women with AGC, HPV positivity strongly correlated with the presence of glandular or squamous cervical lesion but did not help distinguishing women with squamous from those with glandular neoplasia.


Assuntos
Carcinoma de Células Escamosas/virologia , Programas de Rastreamento/métodos , Papillomaviridae/isolamento & purificação , Doenças do Colo do Útero/virologia , Neoplasias do Colo do Útero/virologia , Adulto , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/epidemiologia , Carcinoma in Situ/virologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/epidemiologia , Sondas de DNA de HPV , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Epiteliais e Glandulares/epidemiologia , Neoplasias Epiteliais e Glandulares/virologia , Neoplasias de Células Escamosas/epidemiologia , Neoplasias de Células Escamosas/virologia , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/virologia , Valor Preditivo dos Testes , Doenças do Colo do Útero/diagnóstico , Doenças do Colo do Útero/epidemiologia , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia
7.
Int J Gynecol Cancer ; 16 Suppl 1: 254-8, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16515600

RESUMO

Proapoptotic molecules have been studied in epithelial ovarian neoplasms as possible indicators of the pathogenetic pathways, as targets for new therapeutic approaches, and as prognostic markers. PTEN and p53 are proteins that have many different regulatory functions, including apoptosis. We have studied their immunohistochemical expression in 70 cases of primary ovarian carcinomas (26 serous, 27 endometrioid, and 17 mucinous) and compared the results with morphologic parameters (histologic grade, subtype) and clinical data (age, stage, tumor size). Statistical analyses showed a significantly higher expression of p53 in histologically high-grade tumors (grades 2 and 3), mainly of the serous subtype. A statistical tendency of higher expression of p53 in older patients (P= 0.08) was also observed. The loss of expression of PTEN was significantly more frequent in grade 1 endometrioid adenocarcinomas. These markers did not show association with volume or stage of the tumor. p53 is associated with serous carcinoma, loss of differentiation, and older patients, whereas PTEN inactivation is an early event in carcinogenesis of the endometrioid subtype, as observed in type I endometrial carcinoma. Our results are in keeping with different pathogenetic pathways in subtypes of ovarian carcinoma, prompting the search for new strategies of prevention and treatment.


Assuntos
Adenocarcinoma/metabolismo , Biomarcadores Tumorais/biossíntese , Neoplasias Ovarianas/metabolismo , PTEN Fosfo-Hidrolase/biossíntese , Proteína Supressora de Tumor p53/biossíntese , Adenocarcinoma/patologia , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia
8.
Cytopathology ; 16(6): 295-302, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16303043

RESUMO

OBJECTIVE: To evaluate the presence of some criteria in cervical smears with atypical glandular cells and their correlation with histological patterns to identify pre-neoplastic and neoplastic lesions. METHODS: Seventy-three women referred with an atypical glandular cell smear, who had undergone conization or hysterectomy, were included in this study. Referral Pap smears were reviewed using the set of 27 cyto-morphological criteria that was correlated with the histological diagnosis. RESULTS: Histological results showed intraepithelial or invasive neoplasia in 35 (48%) cases and benign lesions in 38 (52%) cases. After logistic regression and decision tree analysis an increased nuclear/cytoplasmic ratio and the presence of dyskeratotic cells were strongly associated with intraepithelial or invasive neoplasia and the differential cyto-morphological criteria for glandular lesions were decreased cytoplasm, irregular nuclear membranes and the presence of nucleoli. CONCLUSION: The analysis of individual cyto-morphological criteria can better predict intraepithelial or invasive neoplasia and differentiate glandular from squamous lesions.


Assuntos
Carcinoma de Células Escamosas/patologia , Colo do Útero/patologia , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Análise de Variância , Estudos Transversais , Citodiagnóstico/métodos , Diagnóstico Diferencial , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Teste de Papanicolaou , Esfregaço Vaginal
9.
Int J Gynecol Cancer ; 14(1): 126-32, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-14764040

RESUMO

UNLABELLED: The aim was to correlate histological findings in cervix lesions to human papillomavirus (HPV), as detected by polymerase chain reaction (PCR). One hundred and seven women with atypical Pap smear were submitted to colposcopic examination, and suspicious images were biopsied. The PCR assay was performed with the primers MY09/11 and GP05/06+ and, as control, the beta-globin gene was amplified. The morphological findings were correlated to HPV positivity: parakeratosis, acanthosis, koilocytotic atypia (KA), binucleation, dyskeratosis, and number of mitoses. From 107 patients, 61 biopsies were taken: 11 chronic cervicitis (CC), 36 cervical intraepithelial neoplasia (CIN) (13 CIN I; 10 CIN II; 13 CIN III), and 14 suggestive for HPV (SHPV). DNA extraction was not possible in eight cases. HPV was found in 35% CC, 77% CIN, and 64% SHPV. The analysis did not indicate any morphological criteria strongly related to HPV. The findings with highest sensitivity for HPV were KA (88.89%) and binucleation (75%), but with low specificity of 29.41 and 52.94%, respectively. The higher predictive positive values (PV+) for HPV were also KA (72.73%) and binucleation (77.14%). Considering KA, dyskeratosis and binucleation together, PV+ was 72.41%. CONCLUSION: Although indicative, none of the studied morphological criteria was always related to PCR virus detection, denoting some limitations for histological diagnosis.


Assuntos
Biópsia/normas , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Infecções Tumorais por Vírus/virologia , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/virologia , Primers do DNA , DNA Viral/análise , Feminino , Humanos , Papillomaviridae/genética , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Sensibilidade e Especificidade
10.
Braz. j. med. biol. res ; 36(9): 1159-1165, Sept. 2003. tab
Artigo em Inglês | LILACS | ID: lil-342854

RESUMO

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 percent of the VIN III lesions, 33.3 and 66.7 percent of superficially invasive carcinomas, and 7.3 and 58.2 percent 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


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Carcinoma in Situ , Carcinoma de Células Escamosas , Papillomaviridae , Proteína Supressora de Tumor p53 , Neoplasias Vulvares , Carcinoma in Situ , Carcinoma de Células Escamosas , Imuno-Histoquímica , Hibridização In Situ , Infecções por Papillomavirus , Estudos Retrospectivos , Proteína Supressora de Tumor p53 , Infecções Tumorais por Vírus , Neoplasias Vulvares
11.
Braz J Med Biol Res ; 36(9): 1159-65, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12937780

RESUMO

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.


Assuntos
Carcinoma in Situ , Carcinoma de Células Escamosas , Papillomaviridae/isolamento & purificação , Proteína Supressora de Tumor p53/análise , Neoplasias Vulvares , Adulto , Carcinoma in Situ/química , Carcinoma in Situ/virologia , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/virologia , Feminino , Humanos , Imuno-Histoquímica , Hibridização In Situ , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , Estudos Retrospectivos , Proteína Supressora de Tumor p53/genética , Infecções Tumorais por Vírus/virologia , Neoplasias Vulvares/química , Neoplasias Vulvares/virologia
12.
Int J Gynecol Cancer ; 13(4): 450-7, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12911721

RESUMO

The purpose of this study is to investigate the expression of p53, c-erbB-2, Ki-67, and angiogenic activity and their correlation with the clinicopathologic characteristics in a series of granulosa cell tumors of the ovary (GCTO). Eighteen GCTO cases assisted at the Department of Obstetrics and Gynecology, School of Medical Science, UNICAMP, after diagnostic confirmation by three pathologists, were submitted to immunohistochemistry for assessment of p53, c-erbB-2, Ki-67, and CD34 expressions. The mean tumor size was 13 cm (range: 4-30 cm). Six (33%) cases presented with extraovarian disease. Thirteen (72%) cases presented some solid diffuse or sarcomatoid pattern and six (33%) moderate or strong atypia. Fourteen cases presented

Assuntos
Antígenos CD34/análise , Biomarcadores Tumorais/análise , Tumor de Células da Granulosa/genética , Antígeno Ki-67/análise , Neoplasias Ovarianas/genética , Receptor ErbB-2/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD34/genética , Biópsia por Agulha , Intervalo Livre de Doença , Feminino , Genes p53/genética , Tumor de Células da Granulosa/mortalidade , Tumor de Células da Granulosa/patologia , Humanos , Imuno-Histoquímica , Antígeno Ki-67/genética , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , Receptor ErbB-2/genética , Medição de Risco , Estudos de Amostragem , Sensibilidade e Especificidade , Análise de Sobrevida
13.
Int J Gynecol Cancer ; 12(6): 720-7, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12445249

RESUMO

The study was designed to evaluate the prognostic importance of clinical and pathologic variables with p53 and Bcl-2 in epithelial ovarian cancer using multivariate analysis. Tumor tissues from 90 patients were analyzed immunohistochemically for p53 and Bcl-2 expression. Hazard ratios were calculated in univariate and multivariate survival analyses. Forty-two (47%) were considered positive for p53 expression and 18 (20%) were positive for Bcl-2. Positive expression for p53 was less frequent in patients in FIGO stage I (22%). Positive staining for Bcl-2 correlated significantly with the histologic type (P < 0.01). No direct correlations could be demonstrated between p53 and Bcl-2 expression and age or histologic grade. In univariate analysis, p53 and Bcl-2 expression were not significantly correlated with overall survival, disease-free survival, or progression time. FIGO stage III and IV and residual disease > or =2 cm3 after first surgery were significantly correlated with poor outcome in univariate analysis. FIGO stage retained their independent prognostic value in multivariate analysis. Neither p53 nor Bcl-2 had any significant influence on outcome in multivariate survival analysis. FIGO stage proved to be the only significant independent prognostic factor in epithelial ovarian cancer, although residual disease remains correlated with disease-free survival.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Ovarianas/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteína Supressora de Tumor p53/genética , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Biomarcadores Tumorais/sangue , Brasil , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Cistadenocarcinoma Papilar/genética , Cistadenocarcinoma Papilar/mortalidade , Cistadenocarcinoma Papilar/patologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Valor Preditivo dos Testes , Prognóstico , Análise de Sobrevida
14.
Int J Gynecol Cancer ; 12(3): 299-303, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12060452

RESUMO

P53 protein function is frequently down-regulated in cervical cancer by complexing with human papillomavirus (HPV) E6 protein, leading to degradation of p53, genomic instability, and mutations. Results are controversial, however, on the prognostic value of p53 protein expression in cervical cancer. In this study, a cohort of 220 Brazilian women with FIGO stage IB-III cervical squamous cell carcinoma (SCC), followed for 5 years, was analyzed for p53 protein expression using immunohistochemistry. The disease-free survival (DFS) and relapse rate were analyzed using univariate (Kaplan-Meier) and multivariable (Cox's proportional hazards model) survival analyses. P53 protein expression was detected in 35% of the patients, including 21% in stage I, 28% in stage II and 51% in stage III of disease. Of 220 women, only 116 completed one of the treatment options standardized by FIGO within 120 days. There was a higher risk of relapse in stage II and III disease, that was not modified by p53 positivity; HR 3.0 (1.3-6.5) to stage II and HR 4.0 (1.9-8.5) to stage III. The multivariate analysis evidenced that p53 expression is not an independent factor exceeding the power of FIGO stage as the single most important determinant of the hazards for disease relapse.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/metabolismo , Recidiva Local de Neoplasia/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Neoplasias do Colo do Útero/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/terapia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Técnicas Imunoenzimáticas , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Neoplasias do Colo do Útero/terapia
15.
Int J Gynecol Cancer ; 12(2): 223-7, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-11975686

RESUMO

Malignant mixed Mullerian tumors (MMMTs) are rare neoplasms. We report the clinical, pathologic, and immunohistochemical features of an MMMT primary of uterine cervix. This lesion was composed of a poorly differentiated epithelial component (cytokeratin positive) and a spindle cell component (vimentin positive) with heterologous (myoblastic) differentiation (focal 1A4 positive). There were also cells with neuroendocrine features that expressed S-100 and chromogranin A. Along with a brief review of this amazing neoplasm, some histogenetic concepts relevant to this case are discussed. To our knowledge this is the first report of a malignant mixed Mullerian tumor of the uterine cervix with neuroendocrine differentiation.


Assuntos
Carcinoma Neuroendócrino/patologia , Tumor Misto Maligno/patologia , Tumor Mulleriano Misto/patologia , Neoplasias do Colo do Útero/patologia , Idoso , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/terapia , Quimioterapia Adjuvante , Feminino , Humanos , Histerectomia , Imuno-Histoquímica , Tumor Misto Maligno/diagnóstico , Tumor Misto Maligno/terapia , Tumor Mulleriano Misto/diagnóstico , Tumor Mulleriano Misto/terapia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/terapia
16.
Braz J Med Biol Res ; 35(4): 425-30, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11960190

RESUMO

The c-myc protein is known to regulate the cell cycle, and its down-regulation can lead to cell death by apoptosis. The role of c-myc protein as an independent prognostic determinant in cervical cancer is controversial. In the present study, a cohort of 220 Brazilian women (mean age 53.4 years) with FIGO stage I, II and III (21, 28 and 51%, respectively) cervical squamous cell carcinomas was analyzed for c-myc protein expression using immunohistochemistry. The disease-free survival and relapse-rate were analyzed using univariate (Kaplan-Meier) survival analysis for 116 women who completed the standard FIGO treatment and were followed up for 5 years. Positive c-myc staining was detected in 40% of carcinomas, 29% being grade 1, 9% grade 2, and 2% grade 3. The distribution of positive c-myc according to FIGO stage was 19% (17 women) in stage I, 33% (29) in stage II, and 48% (43) in stage III of disease. During the 60-month follow-up, disease-free survival in univariate (Kaplan-Meier) survival analysis (116 women) was lower for women with c-myc-positive tumors, i.e., 60.5, 47.5 and 36.6% at 12, 36, and 60 months, respectively (not significant). The present data suggest that immunohistochemical demonstration of c-myc does not possess any prognostic value independent of FIGO stage, and as such is unlikely to be a useful prognostic marker in cervical squamous cell carcinoma.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/metabolismo , Proteínas Proto-Oncogênicas c-myc/análise , Neoplasias do Colo do Útero/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico
17.
Braz. j. med. biol. res ; 35(4): 425-430, Apr. 2002. ilus, tab
Artigo em Inglês | LILACS | ID: lil-309198

RESUMO

The c-myc protein is known to regulate the cell cycle, and its down-regulation can lead to cell death by apoptosis. The role of c-myc protein as an independent prognostic determinant in cervical cancer is controversial. In the present study, a cohort of 220 Brazilian women (mean age 53.4 years) with FIGO stage I, II and III (21, 28 and 51 percent, respectively) cervical squamous cell carcinomas was analyzed for c-myc protein expression using immunohistochemistry. The disease-free survival and relapse-rate were analyzed using univariate (Kaplan-Meier) survival analysis for 116 women who completed the standard FIGO treatment and were followed up for 5 years. Positive c-myc staining was detected in 40 percent of carcinomas, 29 percent being grade 1, 9 percent grade 2, and 2 percent grade 3. The distribution of positive c-myc according to FIGO stage was 19 percent (17 women) in stage I, 33 percent (29) in stage II, and 48 percent (43) in stage III of disease. During the 60-month follow-up, disease-free survival in univariate (Kaplan-Meier) survival analysis (116 women) was lower for women with c-myc-positive tumors, i.e., 60.5, 47.5 and 36.6 percent at 12, 36, and 60 months, respectively (not significant). The present data suggest that immunohistochemical demonstration of c-myc does not possess any prognostic value independent of FIGO stage, and as such is unlikely to be a useful prognostic marker in cervical squamous cell carcinoma


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Biomarcadores Tumorais , Carcinoma de Células Escamosas , Proteínas Proto-Oncogênicas c-myc , Neoplasias do Colo do Útero , Idoso de 80 Anos ou mais , Estudos de Coortes , Intervalo Livre de Doença , Seguimentos , Imuno-Histoquímica , Valor Preditivo dos Testes , Prognóstico
18.
An. Acad. Nac. Med ; 158(1): 23-6, jun. 1998.
Artigo em Português | LILACS | ID: lil-225673

RESUMO

O carcinoma do colo uterino é, ainda hoje, uma das neoplasias de maior incidência e prevalência entre a populaçäo feminina brasileira, sendo a quarta causa de óbito por câncer entre as mulheres do Estado de Säo Paulo. O carcinoma microinvasor ou estádio la da FIGO, corresponde à fase em que säo detectados os sinais mais precoces de invasäo do estroma cervical e têm-se observado, na literatura, muitas controvérsias quanto aos critérios de definiçäo da doença. Após revisäo da literatura nacional e internacional sobre o assunto, os autores discorrem acerca dos aspectos epidemiológicos de maior relevância sobre o carcinoma microinvasor do colo uterino


Assuntos
Humanos , Feminino , Adulto , Carcinoma , Neoplasias do Colo do Útero/epidemiologia , Útero
19.
Rev. Assoc. Med. Bras. (1992) ; 43(1): 21-4, jan.-mar. 1997. ilus, tab
Artigo em Português | LILACS | ID: lil-188393

RESUMO

Objetivo. A metaplasia tubária (MT) endocervical é uma lesao benigna, classificada como pseudoneoplásica, que tem sido confundida com o adenocarcinoma in situ. Caracteriza-se pela substituiçao do epitélio mucoso endocervical por três tipos celulares: ciliado, secretor e intercalar. O objetivo deste trabalho é localizar e caracterizar morfologicamente a MT no colo uterino, relacionando-a a outras lesoes. Métodos. Os autores selecionaram 18 espécimes de colo uterino com o diagnóstico de MT, obtidos por conizaçao (8 casos) ou histerectomia (10 casos). Dividiram a endocérvice em regioes superior, inferior, epitélio de revestimento superficial e glandular, para observar a freqüência da MT nesses locais. Todos os casos estavam associados a outras lesoes neoplásicas e nao-neoplásicas. Resultados. A MT ocorreu em pacientes de 24 a 72 anos (média = 44 anos). Na maioria (83 por cento), foi encontrada na regiao endocervical superior. Entretanto, em 61 por cento dos casos, também ocorreu nas porçoes mais inferiores do canal, tanto no epitélio de revestimento superficial como em glândulas. Em 60 por cento, houve associaçao da MT com neoplasia intra-epitelial ou invasiva, escamosa ou glandular. Conclusao. Apesar de ser mais freqüente na porçao endocervical superior, a MT também foi identificada nas regioes mais inferiores em mais da metade dos casos estudados, em que pode ser confundida com o adenocarcinoma in situ. Embora comumente associada à neoplasia nesse material, os autores nao podem afirmar qual a freqüência geral da MT no colo uterino e enfatizam a importância do reconhecimento morfológico da lesao.


Assuntos
Adulto , Pessoa de Meia-Idade , Humanos , Feminino , Colo do Útero/patologia , Metaplasia/patologia , Carcinoma in Situ/patologia , Diagnóstico Diferencial , Neoplasias do Colo do Útero/patologia
20.
Rev. Assoc. Med. Bras. (1992) ; 41(3): 236-8, maio-jun. 1995. tab
Artigo em Português | LILACS | ID: lil-156303

RESUMO

A nova classificaçäo por estádios apra o câncer do corpo uterino adotado pela Federaçäo Internacional de Ginecologia e Obstetrícia (FIGO), em 1988, é baseada no exame anatomopatológico intra-operatório da peça de histerectomia, näo irradiada. Objetivo. Através do estudo intra-operatório com a biópsia de congelaçäo, reconhecer os fatores de risco para metástases ganglionares intra-abdominais e selecionar as pacientes que realmente devem ser submetidas à linfadenectomia da ilíaca comum e periaórtica. Métodos. Säo considerados fatores de maior risco para metástase: neoplasias pouco diferenciadas (grau histológico 3), invasäo miometrial profunda (mais da metade do miométrio), tipos histológicos especiais mais agressivos e extensäo da neoplasia ao colo uterino. O exame intra-operatório dura cerca de 30 minutos, quando o útero é aberto lateralmente e säo feitos vários cortes transversais completos para selecionar as áreas suspeitas de maior invasäo miometrial e cervical. Posteriormente, säo comparados os dados do exame de congelaçäo com as lâminas permanentes, em cortes de parafina. REsultados. A comparaçäo dos dados preliminares intra-operatórios com os preparados permanentes revelou alta taxa de concordância, ao redor de 90 por cento, para as diferentes variáveis estudadas. Conclusäo. O procedimento proposto pela FIGO para a nova classificaçäo de estádios do câncer do corpo uterino está sendo avaliado. A alta taxa de concordância encontrada fala a favor da confiabilidade do exame intra-operatório e da sua execuçäo. Tratamento radioterápico complementar é indicado conforme o estádio da doença. Como é um procedimento recente, somente mediante avaliaçäo uniforme dos estádios e protocolos de tratamento poderemos melhor avaliar estas modificaçöes


Assuntos
Humanos , Feminino , Neoplasias do Endométrio/patologia , Linfonodos/patologia , Técnicas Histológicas , Metástase Neoplásica/patologia , Miométrio/patologia , Estadiamento de Neoplasias/classificação , Prognóstico , Fatores de Risco
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