Assessment of Preoperative Endometrial Histopathological Sampling as a Predictor of Final Surgical Pathology in Endometrial Cancer.

OBJECTIVE: To evaluate the agreement between the histopathological diagnoses of preoperative endometrial samples and surgical specimens and correlate the agreement between the diagnoses with the impact on surgical management and the survival of patients with endometrial adenocarcinomas. METHODS: Sixty-two patients treated for endometrial cancer at a university hospital from 2002 to 2011 were retrospectively evaluated. The histopathological findings of preoperative endometrial samples and of surgical specimens were analyzed. The patients were subjected to hysterectomy as well as adjuvant treatment, if necessary, and clinical follow-up, according to the institutional protocol. Lesions were classified as endometrioid tumor (type 1) grades 1, 2, or 3 or non-endometrioid carcinoma (type 2). RESULTS: The agreement between the histopathological diagnoses based on preoperative endometrial samples and surgical specimens was fair (Kappa: 0.40; p < 0.001). However, the agreement was very significant for tumor type and grade, in which a higher concordance occurred at a higher grade. The percentage of patients with lymph nodes affected was 19.2%. Although most patients presenting with disease remission or cure were in the early stages (90.5%), there were no significant differences between those patients who had a misdiagnosis (11/16; 68.8%) and those who had a correct diagnosis (25/33; 75.8%) based on preoperative endometrial sampling (p = 0.605). CONCLUSION: Our findings corroborate the literature and confirm the under staging of preoperative endometrial samples based on histopathological assessment, especially for lower grade endometrial tumors. We suggest that the preoperative diagnosis should be complemented with other methods to better plan the surgical management strategy.

OBJETIVO: Avaliar a concordância entre os diagnósticos histopatológicos de amostras endometriais pré-operatórias e cirúrgicas de pacientes com adenocarcinomas endometriais e avaliar o impacto da concordância entre os diagnósticos no planejamento cirúrgico e sobrevida das pacientes. MéTODOS: Dados de 62 pacientes com câncer de endométrio operadas entre 2002 a 2011 em um hospital universitário foram avaliadas retrospectivamente. As pacientes foram submetidas à histerectomia e tratamento adjuvante, se necessário, e acompanhadas clinicamente de acordo com o protocolo institucional. Foram avaliados os resultados das análises histopatológicas das amostras endometriais pré-operatórias e cirúrgicas. As lesões foram classificadas como tumor endometrioide (tipo 1) graus 1, 2 ou 3 ou carcinoma não endometrioide (tipo 2). RESULTADOS: De modo geral, houve uma concordância baixa entre os diagnósticos histopatológicos das amostras endometriais pré-operatórias e cirúrgicas (Kappa: 0,40; p < 0,001). Entretanto, uma alta concordância entre os diagnósticos foi observada nos tumores de graus mais elevados. Comprometimento de linfonodos ocorreu em 19,2% das pacientes e a maioria das que apresentaram remissão ou cura foram diagnosticadas nos estágios iniciais da doença (90,5%). Não houve diferença significativa na taxa de remissão ou cura entre as pacientes que tiveram concordância (25/33; 75,8%) ou divergência (11/16; 68,8%) entre os resultados histopatológicos pré-operatórios e cirúrgicos (p = 0,605). CONCLUSãO: Nossos achados corroboram a literatura e confirmam o sub-estadiamento de amostras endometriais pré-operatórias com base na avaliação histopatológica, especialmente para tumores endometriais de baixo grau. Outros métodos complementares são necessários para um diagnóstico pré-operatório mais preciso a fim de melhorar o planejamento cirúrgico.

Canonical and noncanonical Wnt pathways: a comparison between endometrial cancer type I and atrophic endometrium in Brazil.

CONTEXT AND OBJECTIVE: The Wnt pathway is involved in tumorigenesis of several tissues. For this reason, we proposed to evaluate Wnt gene expression in endometrial cancer type I. DESIGN AND SETTING: Cross-sectional study on materials gathered from the tissue bank of the Department of Pathology, Universidade Federal de São Paulo. METHODS: Endometrial specimens were obtained from surgeries performed between 1995 and 2005 at São Paulo Hospital, Universidade Federal de São Paulo. The material was divided into two groups according to tissue type: Group A, atrophic endometrium (n = 15); and Group B, endometrial adenocarcinoma (n = 45). We compared the immunohistochemical expression of Wnt1, Frizzled-1 (FZD1), Wnt5a, Frizzled-5 (FZD5) and beta-catenin between endometrial cancer type I and atrophic endometrium. RESULTS: Regarding Wnt1, FZD1 and Wnt5a expression, no significant association was observed between the groups. A significant association was observed between the groups in relation to FZD5 expression (P = 0.001). The proportion of FZD5-positive samples was significantly higher in group A (80.0%) than in group B (31.1%). Regarding the survival curve for FZD5 in group B, we did not find any significant association between atrophic endometrium and endometrial adenocarcinoma. We also did not find any significant association regarding beta-catenin expression (P = 1.000). CONCLUSION: FZD5 is downregulated in endometrial adenocarcinoma, in comparison with atrophic endometrium.

Canonical and noncanonical Wnt pathways: a comparison between endometrial cancer type I and atrophic endometrium in Brazil / Vias Wnt canônica e não canônica: uma comparação entre o câncer endometrial tipo I e endométrio atrófico no Brasil

CONTEXT AND OBJECTIVE: The Wnt pathway is involved in tumorigenesis of several tissues. For this reason, we proposed to evaluate Wnt gene expression in endometrial cancer type I. DESIGN AND SETTING: Cross-sectional study on materials gathered from the tissue bank of the Department of Pathology, Universidade Federal de São Paulo. METHODS: Endometrial specimens were obtained from surgeries performed between 1995 and 2005 at São Paulo Hospital, Universidade Federal de São Paulo. The material was divided into two groups according to tissue type: Group A, atrophic endometrium (n = 15); and Group B, endometrial adenocarcinoma (n = 45). We compared the immunohistochemical expression of Wnt1, Frizzled-1 (FZD1), Wnt5a, Frizzled-5 (FZD5) and beta-catenin between endometrial cancer type I and atrophic endometrium. RESULTS: Regarding Wnt1, FZD1 and Wnt5a expression, no significant association was observed between the groups. A significant association was observed between the groups in relation to FZD5 expression (P = 0.001). The proportion of FZD5-positive samples was significantly higher in group A (80.0 percent) than in group B (31.1 percent). Regarding the survival curve for FZD5 in group B, we did not find any significant association between atrophic endometrium and endometrial adenocarcinoma. We also did not find any significant association regarding beta-catenin expression (P = 1.000). CONCLUSION: FZD5 is downregulated in endometrial adenocarcinoma, in comparison with atrophic endometrium.

CONTEXTO E OBJETIVO: A via Wnt está envolvida na tumorigênese de diversos tipos de tecidos. Por essa razão, propusemo-nos a avaliar a expressão de genes da família Wnt no câncer endometrial tipo I. TIPO DE ESTUDO E LOCAL: Estudo transversal com coleta de materiais do banco de tecidos do Departamento de Patologia da Universidade Federal de São Paulo. MÉTODOS: Amostras endometriais foram obtidas de cirurgias que ocorreram entre 1995 e 2005 no Hospital São Paulo, Universidade Federal de São Paulo. Foram separados dois grupos segundo o tipo de tecido obtido: grupo A, com endométrio atrófico (n = 15); e grupo B, com adenocarcinoma endometrial (n = 45). Comparamos a expressão imunoistoquímica de Wnt 1, Frizzled-1 (FZD1), Wnt 5a, Frizzled-5 (FZD 5) e beta-catenina entre câncer endometrial tipo I e endométrio atrófico. RESULTADOS: Na expressão do Wnt1, FZD1 e Wnt5a, não observamos associação significante entre os grupos. Na expressão do FZD5, encontramos associação significante entre os grupos (P = 0,001). A proporção de positividade do FZD5 foi significantemente maior no grupo A comparado ao grupo B (31,1 por cento). Em relação à curva de sobrevida para o FZD5 no grupo B, não tivemos associação significante entre endométrio atrófico e adenocarcinoma do endométrio. Também não observamos associação significante na expressão da beta-catenina (P = 1,000). CONCLUSÃO: FZD5 é downregulated no adenocarcinoma endometrial quando comparado ao endométrio atrófico.

Reduzindo as incertezas sobre os efeitos da quimiorradioterapia para o câncer do colo do útero: metanálise de dados individuais / Reducing uncertainty about the effects of chemoradiotherapy for cancer of the cervix: a meta-analysis of individual data

Esta é uma excelente metanálise do tratamento do câncer do colo uterino localmente avançado. A revisão ratificou o melhor resultado do tratamento da radioterapia associada à quimioterapia sensibilizante em relação à radioterapia, especialmente quanto à sobrevida e ao intervalo livre de doença.

Canonical and noncanonical Wnt pathway: a comparison among normal ovary, benign ovarian tumor and ovarian cancer.

The Wnt family is involved in tumorigenesis of several tissues. In ovarian cancer, the role played by Wnts and its pathways is not clearly defined. In order to analyze the canonical and noncanonical Wnt pathway in normal ovary, benign ovarian tumor and ovarian cancer, we evaluated the immunohistochemical expression of Wnt1, Frizzled-1 (FZD1), Wnt5a, Frizzled-5 (FZD5) and beta-catenin. Ovarian specimens were obtained from surgeries performed between 1993 and 2004. The patients were divided in three groups: group A, epithelial ovarian cancer (n=38); group B, benign epithelial neoplasia (n=28); and group C, normal ovaries (n=26). Immunoreactivity for Wnt1, FZD1, Wnt5a, FZD5 and beta-catenin was scored for each group. The proportion of Wnt1 positive women in group A (29.4%) was significantly higher than in group B (4.3%) and C (9.1%) (p=0.020). The proportion of FZD1 positive patients in group C (54.5%) was significantly lower than in group A (97.1%) and B (90.0%) (p<0.001). The proportion of Wnt5a positive women was significantly higher for group A (80.0%) compared to group B (25.0%) and C (27.3%) (p<0.001). The proportion of beta-catenin positive patients in group C (95.8%) was significantly higher than group B (52.4%) (p=0.004). Comparison of the survival curves in group A according to Wnt5a expression showed a significant difference between positive and negative patients, whereas the Wnt5a positive women showed worse results (p=0.050). Our findings suggest that the pathways related to Wnt5a have an important role in ovarian malignant neoplasia. Furthermore, Wnt5a was found to be a predictor of poor prognosis for ovarian cancer.

Analysis of the expression of estrogen receptor, progesterone receptor and chicken ovalbumin upstream promoter-transcription factor I in ovarian epithelial cancers and normal ovaries.

Sex hormones are involved in the carcinogenesis of some gynecologic cancers, and the status of their receptors represents an indicator of prognosis and of the therapeutic response in breast and endometrial cancers. In the ovary, this role is not clearly defined, with epithelial cancers being poorly responsive to hormone therapy. COUP-TFI (chicken ovalbumin upstream promoter-transcription factor I) is an orphan nuclear receptor, which is expressed in various tissues and regulates the estrogen receptor (ER) by competition for DNA binding. To investigate the role of these receptors in ovarian carcinogenesis and their implications for cancer prognosis, we evaluated the immunohistochemical expression of ER, progesterone receptor (PR) and COUP-TFI in benign and malignant ovarian epithelial neoplasms and in normal ovaries. A total of 113 ovarian specimens, including 40 diagnosed as malignant epithelial neoplasms (group A), 45 as benign epithelial tumors (group B), and 28 from normal ovaries (group C) were analyzed. Immunoexpression of ER was observed in 70% of patients of group A, 57.8% of group B and 57.1% of group C, with no significant difference between groups (p=0.426). Immunoexpression of PR was significantly lower in group A (12.5%) compared to group B (42.2%) and group C (32.1%) (p=0.010). Similarly, COUP-TFI was expressed in only 10% of group A patients, a rate significantly lower than that observed for group B (31.1%) and group C (39.3%) (p=0.014). No association was observed between the expression of these markers and increased survival or clinical prognostic variables. Multivariate analysis revealed a residual tumor <1 cm as the most significant clinical prognostic factor in group A (p=0.010, OR=4.14). These data support the importance of cytoreduction in the treatment of ovarian cancer, the role of steroid receptors in the mechanism of carcinogenesis, and the need for selection of subgroups that may respond to hormone therapy.

Neoplasia "borderline" do ovário e gestação: relato de caso / Ovary borderline tumor with pregnancy: a case report

Os autores relatam um caso de uma paciente de 35 anos de idade, tercípara e com história de incompetência istmo-cervical que, durante exames obstétricos iniciais, apresentou massa pélvica à esquerda. A paciente foi encaminhada para o departamento de diagnóstico por imagem, onde se submeteu a avaliação por ultra-sonografia e ressonância magnética. Foi indicada a cirurgia e o tumor foi ressecado, com diagnóstico final de cistadenoma seroso borderline ou de baixo potencial de malignidade. Os principais achados de imagem são descritos e discutidos, associados com breve revisão de literatura.

A case of borderline serous cystadenoma in a 35 years pregnancy woman with previous history of cervix incompetence is reported. This tumor was discovered during initial obstetric exams, and evaluated by ultrasound and magnetic resonance imaging scans. Theauthors describe the clinical and diagnostic finding with a brief review of the literature.

Effects of tamoxifen therapy on the expression of p27 protein in the endometrium of women with primary breast cancer.

The cyclin-dependent kinase inhibitor, p27, has been shown to mediate cell growth arrest thereby significantly reducing the percentage of proliferating cells. It seems that p27 expression is essential for the control of normal endometrial proliferation, and reduced or absent p27 expression may be an important step in endometrial carcinogenesis. Our aim was to demonstrate the effects of tamoxifen therapy on the expression of p27 protein in the endometrium of postmenopausal breast cancer patients. Fifty-three pre- and post-tamoxifen treatment endometrium samples were examined immunohistochemically using p27 antibody. Tamoxifen therapy (20 mg/day) for 60 days increased the expression of p27 protein in the endometrium of postmenopausal breast cancer patients. We conclude that tamoxifen therapy does not seem to be directly involved in the carcinogenesis of endometrial carcinoma since the expression of p27 is not decreased.

Comparaçäo entre a histerossonografia, a histeroscopia e a histopatologia na avaliaçäo da cavidade uterina de mulheres na pós-menopausa / Comparison between hysterosonography, hysteroscopy and histopathology in the evaluation of postmenopausal woman uterine cavity

Objetivo: comparar os resultados da histerossonografia com os da histeroscopia e com os da histopatologia em mulheres na pós-menopausa. Métodos: realizou-se histerossonografia, histeroscopia e biópsia endometrial dirigida em 58 mulheres que tinham eco endometrial maior que 4 mm, idade superior a 40 anos, tempo de amenorréia superior a um ano e níveis de hormônio folículo estimulante maiores que 35 mUI/mL. Foram excluídas as pacientes que fizeram uso de hormonioterapia, assim como aquelas com fatores que impedissem a realizaçäo dos exames de histerossonografia, histeroscopia ou o estudo histopatológico. A análise estatística foi obtida pelos testes G de Cochran e McNemar. Foram calculados cálculados os valores de sensibilidade, especificidade e preditivos positivo e negativo da histerossonografia comparados com os outros exames. Resultados: as taxas de concordância da histerossonografia comparada aos achados histeroscópicos e histológicos foram de 94,8 e 77,6 por cento, respectivamente. A sensibilidade e a especificidade na detecçäo de anormalidade da cavidade endometrial da histerossonografia comparadas com a histeroscopia foram de 98 e de 75 por cento, respectivamente. Já os valores preditivos positivo e negativo da histerossonografia foram de 96 e de 86 por cento, respectivamente. Na comparaçäo ao estudo histopatológico para o diagnóstico de alterações da cavidade endometrial, a histerossonografia revelou sensibilidade de 98 por cento, especificidade de 33 por cento e os valores preditivos positivo e negativo foram de 76 e de 86 por cento, respectivamente. Ressalta-se que das onze pacientes com sinéquia uterina diagnosticada pela histerossonografia, duas tiveram hiperplasia endometrial. Houve um caso de cavidade normal pela histerossonografia em que o resultado da biópsia foi hiperplasia endometrial simples. Conclusões: nossos dados sugerem que a histerossonografia tem boa sensibilidade comparada com a histeroscopia. Contudo, há limitações deste método diagnóstico comparado com o histopatológico, principalmente nos casos de sinéquia uterina

[Histopathological and immunohistochemical analysis (proliferating cel nuclear antigen) of patients with invasive cervical carcinoma before and after radiotherapy and surgery]. / Análise histopatológica e imuno-histoquímica (antígeno nuclear de proliferação cellular) de pacientes com carcinoma cervical invasor antes e após radioterapia e cirurgia.

OBJECTIVE: To search for residual disease and to analyse the Proliferating Cellular Nuclear Antigen (PCNA) status, in patients with cervical squamous cell carcinoma, treated with both radiotherapy and surgery. METHODS: Histological slides from 16 patients with uterine cervix cancer, treated between April 1986 and August 1998, with preoperative radiotherapy and surgery, were reviewed. PCNA immunohistochemical reactivity of these samples was evaluated, using the IMAGELAB 2.3 computer image analysis system. RESULTS: Residual carcinoma were found in eight cases (50%) and no malignant features was found in eight cases (50%). The mean value of PCNA before radiotherapy in patients with residual cancer was 61.56% and in cases without residual cancer was 60%. Its expression before radiotherapy was between 27.91% and 89.93% (60% average), while after radiotherapy it varied between 55.80% and 86.73% (74% average). CONCLUSIONS: The association between preoperative radiotherapy followed by surgery is adequate to treat patients with cervical cancer, when radical treatment is not possible. Meanwhile, exclusive radiotherapy shows a significant failure rate, detected after surgery and PCNA analysis.

Análise histopatológica e imuno-histoquímica (antígeno nuclear de proliferaçäo celular) de pacientes com carcinoma cervical invasor antes e após radioterapia e cirurgia / Histopathological and immunohistochemical analysis (proliferating cell nuclear antigen) of patients with invasor cervical carcinoma before and radiotherapy and surgery

OBJETIVO: Avaliar a existência de tumor residual e o índice de proliferaçäo celular (PCNA) em pacientes com carcinoma espinocelular do colo uterino, tratadas com a combinaçäo de radioterapia e cirurgia. MÉTODOS: Avaliamos 16 pacientes com carcinoma do colo uterino atendidas no período de abril de 1986 a agosto de 1998, tratadas com irradiaçäo pré-operatória e cirurgia. Após revisäo histopatológica do material das biópsias e peças cirúrgicas, procedeu-se ao exame imuno-histoquímico para avaliar a expressäo do PCNA. A imuno-expressäo do PCNA foi analisada através do programa de análise gráfica por computador IMAGELAB 2.3. RESULTADOS: Em oito (50 por cento) casos detectou-se persistência de neoplasia e em outros oito (50 por cento) houve ausência de neoplasia residual. O valor médio do índice de PCNA anterior à radioterapia nos casos com tumor residual foi de 61,56 por cento e, nos casos sem tumor residual, de 60 por cento. A avaliaçäo da expressäo do PCNA nas 16 biópsias prévias à radioterapia mostrou valor médio de 60 por cento. Nas peças de histerectomia com neoplasia residual a expressäo do PCNA foi, em média, 74 por cento. CONCLUSÖES: A associaçäo de radioterapia pré-operatória e cirurgia no carcinoma do colo uterino permite adequada terapêutica em pacientes sem condiçöes para a cirurgia radical. Outrossim, a radioterapia exclusiva apresenta percentagem relevante de insucessos detectados pela cirurgia e pela análise do PCNA

Avaliaçäo endometrial em mulheres menopausadas com câncer de mama: Estudo histeroscópico e anátomo-patológico / Endometrial evaluation in post-menopausal women with breast cancer

Estudou-se o endométrio de mulheres pós-menopáusicas com câncer de mama, comparando-as com menopausadas assintomáticas, para avaliar as diferenças na freqüencia de afecçöes endometriais. Avaliou-se o endométrio de 168 pacientes, sendo 67 com câncer de mama e 101 mulheres normais, de janeiro a dezembro de 1996, por meio da histeroscopia ambulatorial com biópsia do endométrio. Nas pacientes com câncer de mama, encontram-se 29,9 por cento de endometrio ativos, sendo dez pólipos endometriais (15,0 por cento), oito endométrios proliferativos (11,9 por cento), um caso de câncer de endométrio (1,5 por cento) e uma hiperplasia endometrial simples sem atipias (1,5 por cento). No grupo controle, houve 8,0 por cento de endométrios ativos, sendo quatro (4,0 por cento) pólipos endometriais e quatro (4,0) endométrios proliferativos. As diferenças foram estatisticamente significativas, principalmente, em enfermas com índice de massa corpórea acima de 27,3. A sensibilidade da histeroscopia foi de 82,14 poe cento, a especificidade, de 97,16 por cento, o valor preditivo positivo, de 85,18 por cento e o valor preditivo negativo, de 96,48 por cento na detecçäo da atividade endometrial. Conclui-se que a avaliçäo endometrial deva ser incluída na propedêutica das pacientes com câncer de mama, principalmente se obesas. A histeroscopia ambulatorial demonstrou ser o método adequado para a avaliaçäo da mucosa uterina dessas enfermas, selecionando a área da cavidade uterina para a biópsia

Aspectos atuais da farmacodinâmica e dos efeitos sistêmicos e ginecológicos do tamoxifeno / Currente aspects about tamoxifen pharmacodynamic and sistemic and gynecologycal effects

O tamoxifeno é a droga de escolha na hormonioterapia adjuvante do câncer de mama, aumentando o tempo livre de doença, a sobrevida e reduzindo o índice de câncer mamário contralateral. Além disso, induz benefícios à saúde como um todo, ao melhorar o perfil lipoprotéico (como conseqüente efeito protetor cardiovascular) e ao manter a mineralizaçao óssea. Utilizado inicialmente na doença metastática, é preconizado nos dias de hoje em todos os estádios de doença. Possui poucos efeitos colaterais; entretanto, em 1985 relataram-se os primeiros casos de câncer de endométrio associado ao seu uso. Ensaios metanalíticos recentes, envolvendo grande número de usuários, mostraram nao haver correlaçao significante entre o uso do tamoxifeno e o desenvolvimento de neoplasia endometrial. No presente estudo, os autores revisam os aspectos atuais da farmacodinâmica da droga e procuram ressaltar seus efeitos sistêmicos e ginecológicos.

Peritoneal borderline cystoadenocarcinoma

Carcinomas of peritoneal origin represent a seldom diagnosed entity of unknown etiology, with important implications in terms of prophylactic oophorectomy. Initially described in patients belonging to families at high risk for ovarian cancer, it possibly has a pathogeny similar to that of endosalpingiosis and of some cases of endometriosis. We report a case of peritoneal borderline mucinous carcinoma with an anatomopathological diagnosis of normal ovaries.

Importance of peniscopy, oncologic cytology and histopathology in the diagnosis of penile infection by human papillomavirus

Introduction: Male genital infection by human papillomavirus is of particular importance since it is often asymptomatic. The patient generally presents no clinical lesion. Therefore, men represent an important reservoir of virus, playing a special role in the transmission and perpetuation of the disease. Patients and methods: In the present prospective clinical trial study, 190 sex partners of women with genital infection by human papillomavirus, associated or not with cervical intraepithelial neoplasia, were investigated. All patients were unaware of or denied the presence of a genital lesion. Results: Cytologic examination revealed koilocytosis in 9 cases (4,7 per cent) in the urethra and in 3 cases (1.6 percent) in the corona of the glans and the distal prepuce. Peniscopy with the previous use of 5 percent acetic acid revealed white lesions in 97,9 per cent of the patients. Toluidine blue stained most to the lesions. At least one fragment revealed koilocytosis in the histopathologic study of 97 cases (51.05 per cent). Conclusion: The three methods complement one another, allowing a more precise diagnosis of this infection in men.