Loss of RKIP expression during the carcinogenic evolution of endometrial cancer

Aims Endometrial cancer is one of the most common cancers in women worldwide, but there is a lack of diagnostic markers for early detection of these tumours. The raf kinase inhibitory protein (RKIP) negatively regulates the Raf/MEK/ERK pathway, and the downregulation of RKIP is associated with tumour progression and metastasis in several human neoplasms. The aim of this study was to assess the expression levels of RKIP in endometrial cancer and determine whether this expression correlates with clinical outcome in these patients.Methods Tissue microarrays constructed using tissue samples from 209 endometrial adenocarcinomas, 49 endometrial polyps and 48 endometrial hyperplasias were analysed for RKIP expression by immunohistochemistry.Results The authors found that RKIP expression decreases significantly during malignant progression of endometrial cancer; it is highly expressed in non-neoplastic tissues (polyps 79.6%; hyperplasias 87.5%) and expressed at very low levels in endometrioid adenocarcinomas (29.7%). No correlations were observed between RKIP expression, clinicopathological data and survival.Conclusion This study demonstrated for the first time that RKIP expression is lost during the carcinogenic evolution of endometrial tumours and that the loss of RKIP expression is associated with a malignant phenotype. Functional studies are needed to address the biological role of RKIP downregulation in endometrial cancer.

Usefulness of Clinical, Ultrasonographic, Hysteroscopic, and Immunohistochemical Parameters in Differentiating Endometrial Polyps From Endometrial Cancer

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Validation of hysteroscopic view in cases of endometrial hyperplasia and cancer in patients with abnormal uterine bleeding

STUDY OBJECTIVE: To validate hysteroscopic view with histology in cases of endometrial hyperplasia and cancer in patients with abnormal uterine bleeding (AUB)DESIGN: Retrospective study.(Canadian Task Force classification II-3).SETTING: University teaching hospitals in Rio de Janeiro and São Paulo, and private office in Rio de Janeiro.PATIENTS: Four thousand and fifty-four patients with AUB in whom hysteroscopic views were complete and the histologic result was conclusive.INTERVENTION: Four thousand and fifty-four office hysteroscopies with complete views and conclusive histologic results. The material for histologic examination was obtained through biopsy of the lesion in an outpatient unit or through the resection of the entire lesion in patients who underwent surgery. Histology was considered the gold standard and compared with the hysteroscopic view.MEASUREMENTS AND MAIN RESULTS: In the histology of the 4054 examinations, 613 (15.2%) were endometrial hyperplasia, and 105 (2.6%) were endometrial cancer. The most frequent hysteroscopic finding was endometrial polyps (31.2%). In endometrial hyperplasia, the sensitivity of the hysteroscopic view was 56.3% (95% CI 52.21-60.2%), specificity was 89.1% (95% CI 88.0%-90.1%), positive predictive value (PPV) was 48.0% (95% CI 44.3%-51.7%), negative predictive value (NPV) was 92.0% (95% Cl 90.1%-92.9%), and accuracy was 72.7% (95% CI 70.7%-74.7%). Accuracy was defined as the proportion of correct results among the hysteroscopic examinations. In endometrial cancer, the sensitivity of the hysteroscopic view was 80.0% (95% Cl 71.1%-87.2%), specificity was 99.5% (95% CI 99.2%-99.7%), PPV was 81.5% (95% Cl 72.7%-88.5%), NPV was 99.5% (95% CI 99.2%-99.7%), and accuracy was 89.8% (95% CI, 85.9%-93.6%). In the 814 patients (20.0%) in whom the hysteroscopic view was normal, there were no false negatives for endometrial cancer; however, there were 37 (4.5%) false negatives for endometrial hyperplasia. In the histologic cases of endometrial cancer, 101 (96.2%) hysteroscopic views were compatible with cancer or hyperplasia (80.0% and 16.2%, respectively). Ninety-seven out of 103 hysteroscopic views with cancer findings (94.2%) had histologic diagnosis of cancer or hyperplasia (81.5% and 12.6%, respectively).CONCLUSION: It seems that even in face of good validity of hysteroscopic view for endometrial hyperplasia and cancer, histologic study is mandatory in the presence of any lesion as the hysteroscopic view cannot completely replace the histologic study in patients with AUB. (C) 2006 AAGL. All rights reserved.

Evaluation of clinical, ultrasonographic and hysteroscopic parameters in the differentiation of endometrial polyps and cancer of endometrium

Study Objective: To evaluate the diagnostic accuracy of transvaginal ultrasound and office hysteroscopy in the differentiation between endometrial polyps and endometrial adenocarcinoma. Design: This is a prospective 100 women longitudinal study, 24 to 80 years, submitted to hysteroscopic polypectomy (n = 80) or surgery due to endometrial adenocarcinoma (n = 20), from january 2010 to December 2011. Clinical, ultrasonographic and hysteroscopic parameters were analyzed and compared with histopathologic find. Statistical analysis were performed utilizing the Tukey, Kruskal-Wallis, Dunn and Mann-Whitney test, with a confidence interval of 95% and p\0, 05 statiscally significant. Setting: Botucatu Medical School. Intervention: Prospective analysis of clinical, ultrasonographic and hysteroscopic parameters in patients with diagnosis suspected of endometrial polyps and adenocarcinoma of endometrium were performed. According to the diagnosis, hysteroscopic polypectomy or pan hysterectomy with lymph node sampling was realized. After the surgery and histopathological study, statistical analysis of parameters was performed and the results were compared between groups. It was Research Ethics Committee approved. Measurements and Main Results: There were no differences between age, BMI, menopause, TH use and associated diseases among groups. The main symptom of endometrial cancer was the postmenopausal bleeding, affecting 84,2% of women against 34,8% of polypectomy group. The majority of women with endometrial polyps were asymptomatic. Transvaginal ultrasonography showed no ability to differentiate cases of endometrial cancer compared with the cases of endometrial polyps, considering the presence of endometrial thickness and blood flow on color Doppler. Office hysteroscopy showed significant changes in 75% of the adenocarcinoma cases, especially the presence of diffuse hypervascularity with atypical vessels. Conclusion: Still remains an inability to establish clinical parameters and reliable ultrasound imaging to differentiate endometrial polyps and cancer of endometrium. Attention should be given to hysteroscopic exams presenting diffuse endometrial hypervascularization with architectural distortion of the vessels. The recommendation of our service remains the systematic removal of all endometrial polyps.

Expression of p53, Ki-67, and CD31 proteins in endometrial polyps of postmenopausal women treated with tamoxifen.

This study was undertaken to investigate the expression of p53, Ki-67, and CD31 proteins in endometrial polyps of postmenopausal women treated with tamoxifen (TAM). Postmenopausal women with endometrial polyps treated with TAM (n = 20), postmenopausal women with endometrial polyps without hormone use (n = 20), postmenopausal women with atrophic endometrium (n = 20), and postmenopausal women with endometrial adenocarcinoma (n = 20) were prospectively investigated. Tissue samples were immunohistochemically evaluated by monoclonal antibodies for p53, Ki-67, and CD31. The data were analyzed using the Student t test, analysis of variance, and χ2 to evaluate significant differences between the groups. The level of significance was set at P < 0.05. There was no difference in the expression of p53 between the groups (P = 0.067). The expression of Ki-67 was higher in the polyp samples from TAM-treated women compared with those from the women using no hormone (P = 0.0047) and those from the women with atrophic endometrium (P = 0.008). Samples from the women with endometrial cancer was associated with higher Ki-67 expression compared with the polyp samples from TAM-treated women (P = 0.004). The expression of CD31 was higher in the polyp samples of TAM-treated women compared with that of the samples from the women with atrophic endometrium (P < 0.001) and similar to the polyp samples from the women using no hormone (P = 0.319) and to the samples from the women with endometrial cancer (P = 0.418). The use of TAM in postmenopausal women might be associated with increased cellular proliferation in endometrial polyps without interfering angiogenesis or inactivation of tumor suppressor proteins.

Prevalence of hysteroscopic findings and histologic diagnoses in patients with abnormal uterine bleeding

Objective: To describe the prevalence of hysteroscopic findings and histologic diagnoses inpatients with abnormal uterine bleeding (AUB).Design: Retrospective series of consecutive patients.Setting: Tertiary care University hospital and private office.Patient(s): Four thousand fifty-four hysteroscopies with biopsy in patients with AUB evaluated between June 1993 and December 2004.Intervention(S): Hysteroscopies were performed using 2.9-mm or 4-mm telescopes with CO2 or saline as the distension media. Biopsies were (lone with a 5-mm grasper or with a Novak's curette.Main Outcome Measure(s): Prevalence of hysteroscopic findings and histologic analysis of biopsies.Result(S): Endometrial polyp was the most frequent hysteroscopic finding, accounting for 1,374 (33.9%) cases. Normal uterine cavity and cervical canal were found in 814 (20.1%) patients. Submucous fibroids were diagnosed in 302 (7.5%) women. Normal endometrium was the most frequent histologic diagnosis, accounting for 1,888 (46.6%) cases. Endometrial polyp was found in 1, 115 (27.5%) patients. Endometrial hyperplasia was diagnosed in 613 (15.1%) and endometrial cancer in 105 (2.6%) women.Conclusion(s): Endometrial polyps are the most frequent hysteroscopic findings in patients with AUB, whereas normal endometrium is the most frequent histologic diagnosis.

Tratamento Clínico e Seguimento das Hiperplasias de Endométrio

Objetivos: avaliar a eficácia do acetato de medroxiprogesterona e do acetato de megestrol nas hiperplasias de endométrio. Métodos: foram incluídas, retrospectivamente 47 pacientes com sangramento uterino anormal, submetidas a curetagem uterina diagnóstica e/ou biópsia de endométrio, cujo achado histopatológico foi de hiperplasia de endométrio. Nas pacientes com hiperplasia sem atipia foi iniciado a terapêutica com acetato de medroxiprogesterona por via oral, na dose de 10 mg/dia durante 10-12 dias por mês. Nas com atipia, era utilizado o acetato de megestrol por via oral, dose de 160 mg/dia, uso contínuo. O período de tratamento variou de 3 a 18 meses. Biópsia de endométrio e/ou curetagem uterina de controle foram realizadas entre três e seis meses do início do tratamento e periodicamente para avaliar a resposta terapêutica. Resultados: foram analisadas 42 pacientes com hiperplasia endometrial sem atipia e cinco com atipia. A média de idade das pacientes foi de 49,5 ± 10,6 anos, sendo 70,2% com idade superior a 45 anos. O acetato de medroxiprogesterona foi eficaz em fazer regredir as hiperplasias sem atipias em 83,2% (35/42) e o acetato de megestrol em 80% (4/5) das hiperplasias com atipia. em 16,8% (7 casos) das hiperplasias sem atipia e em 20% (1 caso) das com atipia, ocorreu persistência das lesões, apesar do tratamento. em nenhum caso ocorreu progressão para câncer de endométrio, durante o período de seguimento que foi de 3 meses a 9 anos. No acompanhamento dessas pacientes, verificamos que 18 (38,3%) apresentaram amenorréia, em 12 (25,5%) ocorreu regularização do ciclo menstrual e 17 (36,2%) permaneceram com sangramento uterino anormal, sendo submetidas a histerectomia total abdominal. O exame anatomopatológico mostrou a persistência da lesão hiperplásica em oito casos, leiomioma em quatro, adenomiose em três, mio-hipertrofia uterina difusa em um caso e útero normal em outro, tendo havido regressão das lesões hiperplásicas nesses últimos nove casos. Conclusões: o tratamento das hiperplasias de endométrio com acetato de medroxiprogesterona e/ou acetato de megestrol, representa uma alternativa satisfatória para mulheres que desejam preservar o útero ou que tenham risco cirúrgico elevado. Entretanto, é necessário monitorização cuidadosa do endométrio, o que deve ser realizado pela avaliação dos sintomas, ultra-sonografia transvaginal e biópsia periódica.

La última palabra en dosis mínima

In this article we rewiewed the indications of the low-dose hormone replacement therapy in post menopausal women. We evaluate the effects of this therapy on menopausal symptoms bone metabolism, cardiovascular risk and endometrial cancer. The low-dose hormone replacement therapy is satisfactory to relief menopausal symptoms and improves lipid profile preventing atherosclerosis. It does not increase the risk of hyperplasia or endometrial cancer when is associate with progestagens. The low dose hormone replacement therapy is also associate to improve bone mineral density but to have better comprehension about the effective action of the low dose hormone replacement therapy on bone, more studies evaluating the risk of fractures are necessary.

Avaliação histeroscópica e imuno-histoquímica dos pólipos endometriais

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Investigação da evolução dos pólipos endometriais em câncer de endométrio

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Low-grade endometrial stromal sarcoma presenting as vaginal nodule

Endometrial stromal sarcoma is a rare neoplasm of the uterus. Extrauterine locations of this neoplasm, excluding metastases or local extension, are even more unusual and are usually associated with the presence of endometriosis. The authors report a case of endometrial stromal sarcoma presenting as a vaginal wall nodule, without any sign of primary uterine tumor after extensive evaluation or presence of endometriosis. The morphology, immunohistochemical profile, differential diagnoses, and pathogenesis are discussed, as well as a review of the literature on this issue. © 2004 Elsevier Inc. All rights reserved.

Claudina-3 e Claudina- 4, potenciais marcadores de agressividade no carcinoma endometrial Tipo I

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB