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1.
Ann Surg Oncol ; 23(1): 171-7, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25952272

RESUMO

BACKGROUND: Additional tools are needed to improve the selection of women with early-stage endometrial cancer (EC) at increased risk of nodal metastases and/or recurrence to adapt surgical staging and adjuvant therapies. The aim of this study was to assess the impact of EC tumor size on nodal status and recurrence-free survival (RFS) according to European risk groups for recurrence. METHODS: Data of 633 women with early-stage EC who received primary surgical treatment between 2001 and 2012 were abstracted from a multicenter database. Optimal tumor size cut-offs were determined by a minimal p value approach according to final nodal status. Logistic regression was used to determine the impact of defined tumor size on nodal involvement, and the Kaplan-Meier method was used to estimate the survival distribution. RESULTS: The number of women with final low-, intermediate-, and high-risk EC was 302, 204, and 127, respectively. Tumor size was correlated with nodal status and RFS in women with low-risk EC, while no correlation was found for women with intermediate/high-risk EC. Tumor size ≥35 mm emerged as the optimal threshold for a higher rate of nodal involvement (odds ratio 4.318, 95 % CI 1.13-16.51, p = 0.03) and a lower RFS (p = 0.005) in women with low-risk EC. CONCLUSION: Tumor size is an independent prognostic factor of lymph node involvement in women with low-risk EC and could be a valuable additional histological criterion for selecting women at increased risk of lymph node metastases to better adapt surgical staging.


Assuntos
Neoplasias do Endométrio/patologia , Excisão de Linfonodo , Recidiva Local de Neoplasia/epidemiologia , Carga Tumoral , Idoso , Neoplasias do Endométrio/cirurgia , Feminino , Seguimentos , França/epidemiologia , Humanos , Incidência , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
2.
Ann Surg Oncol ; 22(13): 4224-32, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25869227

RESUMO

BACKGROUND: This study aimed to develop a predictive model using histopathologic characteristics of early-stage type 1 endometrial cancer (EC) to identify patients at high risk for lymph node (LN) metastases. METHODS: The data of 523 patients who received primary surgical treatment between January 2001 and December 2012 were abstracted from a prospective multicenter database (training set). A multivariate logistic regression analysis of selected prognostic features was performed to develop a nomogram predicting LN metastases. To assess its accuracy, an internal validation technique with a bootstrap approach was adopted. The optimal threshold in terms of clinical utility, sensitivity, specificity, negative predictive values (NPVs), and positive predictive values (PPVs) was evaluated by the receiver-operating characteristics (ROC) curve area and the Youden Index. RESULTS: Overall, the LN metastasis rate was 12.4 % (65/523). Lymph node metastases were associated with histologic grade, tumor diameter, depth of myometrial invasion, and lymphovascular space involvement status. These variables were included in the nomogram. Discrimination of the model was 0.83 [95 % confidence interval (CI) 0.80-0.85] in the training set. The area under the curve ROC for predicting LN metastases after internal validation was 0.82 (95 % CI 0.80-0.84). The Youden Index provided a value of 0.2, corresponding to a cutoff of 140 points (total score in the algorithm). At this threshold, the model had a sensitivity of 0.73 (95 % CI 0.62-0.83), a specificity of 0.84 (95 % CI 0.82-0.85), a PPV of 0.40 (95 % CI 0.34-0.45), and an NPV of 0.95 (95 % CI 0.94-0.97). CONCLUSION: The results show that the risk of LN metastases can be predicted correctly so that patients at high risk can benefit from adapted surgical treatment.


Assuntos
Neoplasias do Endométrio/patologia , Modelos Teóricos , Miométrio/patologia , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/cirurgia , Feminino , Seguimentos , Humanos , Excisão de Linfonodo , Metástase Linfática , Pessoa de Meia-Idade , Miométrio/cirurgia , Invasividade Neoplásica , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Nomogramas , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Medição de Risco , Taxa de Sobrevida , Carga Tumoral
3.
Gynecol Oncol ; 136(1): 112-20, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25449309

RESUMO

OBJECTIVE: DNA repair mechanisms, environment-mediated drug resistance and cancer initiating cells (CIC) are three major research concepts that can explain the chemoresistance of epithelial ovarian cancer (EOC). The objective was to test if changes in the expression of potential markers associated with drug resistance before and after chemotherapy would correlate with platinum resistance, defined as a recurrence within the first year after chemotherapy cessation, and with survival, in advanced EOC. METHODS: We included 32 patients with stage IIIC-IV EOC who underwent laparoscopy to evaluate the extent of carcinomatosis, neoadjuvant chemotherapy (carboplatin/taxol) and interval surgery. Biopsies taken during the initial laparoscopies and interval surgeries were evaluated using immunohistochemistry for the expression of 7 proteins: CD117, CD44 and ALDH1 to evaluate CIC; IL-6, IL-8 and BMP2 to evaluate environment-mediated drug resistance; and ERCC1 to evaluate DNA repair. Expression measurements were correlated with platin resistance and survival. The markers' relevance was confirmed in vitro using chemoresistance tests and flow cytometric measurements of the proportion of CD44+ cells. RESULTS: 17 patients were chemoresistant and 15 patients were chemosensitive. We observed increases in CD44, IL-6 and ERCC1 expression and stable ALDH1, CD117, IL-8, and BMP2 expression. Reduced expression of cancer initiating cell markers and increased expression of environment-mediated drug resistance markers were associated with poor prognosis. We also demonstrated that CD44+ cells had survival advantages in vitro. CONCLUSIONS: Changes in CD44 and IL-8 expression on tumor cells appeared to correlate with overall survival and should be further tested as predictors of chemoresistance using larger cohort.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carcinoma Epitelial do Ovário , Quimioterapia Adjuvante , Proteínas de Ligação a DNA/metabolismo , Resistencia a Medicamentos Antineoplásicos , Endonucleases/metabolismo , Feminino , Humanos , Receptores de Hialuronatos/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Paclitaxel/administração & dosagem
4.
Am J Obstet Gynecol ; 212(1): 56.e1-7, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24983678

RESUMO

OBJECTIVE: The objective of the study was to externally validate and assess the robustness of 2 nomograms designed to predict the probability of lymphatic dissemination (LD) for patients with early-stage endometrioid endometrial cancer. STUDY DESIGN: Using a prospective multicenter database, we assessed the discrimination, calibration, and clinical utility of 2 nomograms in patients with surgically treated early-stage endometrioid endometrial cancer. RESULTS: Among the 322 eligible patients identified, the overall LD rate was 9.9% (32 of 322). Predictive accuracy according to discrimination was 0.65 (95% confidence interval, 0.61-0.69) for the full nomogram and 0.71 (95% confidence interval, 0.68-0.74) for the alternative nomogram. The correspondence between observed recurrence rate and the nomogram predictions suggests a moderate calibration of the nomograms in the validation cohort. CONCLUSION: The nomograms were externally validated and shown to be partly generalizable to a new and independent patient population. Although these tools provide a more individualized estimation of LD, additional parameters are needed to allow higher accuracy for counseling patients in clinical practice.


Assuntos
Carcinoma Endometrioide/secundário , Neoplasias do Endométrio/patologia , Metástase Linfática , Nomogramas , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos
5.
Gynecol Endocrinol ; 31(4): 282-5, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25495249

RESUMO

The risk of endometrial hyperplasia (EH) progressing into endometrioid endometrial cancer ranges from 1% for simple EH without atypia (EHWA) to 46.2% for atypical EH (AEH). Differentiation between both entities is crucial to determine optimal management. As preoperative diagnosis of AEH can be difficult, we aimed to establish clusters of immunohistochemical markers to distinguish EHWA from AEH. We studied 13 immunohistochemical markers (steroid receptors, pro/anti-apoptotic proteins, metalloproteinases (MMP), tissue inhibitor of metalloproteinase (TIMP), CD44 isoforms) known for their role in endometrial pathology. Using supervised clustering, we determined clusters of co-expressed proteins which contributed the most in differentiating EHWA from AEH. From 39 tissue samples (17 EHWA and 22 AEH), we found three clusters of co-expressed proteins: Cluster 1 included two proteins (over-expression of estrogen receptor (ER) and under-expression of progesterone receptor (PR) B in AEH compared to EHWA); Cluster 2: an ER, PR A, MMP-2 and TIMP-1 over-expression and a PR B and TIMP-2 under-expression; Cluster 3: over-expression of ER and MMP-7 and under-expression of PR B and TIMP-2. AEH can be accurately distinguished from EHWA using a supervised clustering of immunohistochemical markers. This promising approach could be useful to improve the preoperative diagnosis of EH.


Assuntos
Hiperplasia Endometrial/diagnóstico , Endométrio/metabolismo , Biomarcadores/metabolismo , Análise por Conglomerados , Diagnóstico Diferencial , Regulação para Baixo , Hiperplasia Endometrial/metabolismo , Hiperplasia Endometrial/patologia , Endométrio/enzimologia , Endométrio/patologia , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 7 da Matriz/metabolismo , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Receptores de Progesterona/metabolismo , Aprendizado de Máquina Supervisionado , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Regulação para Cima
6.
Gynecol Oncol ; 133(2): 205-10, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24556060

RESUMO

OBJECTIVES: Differentiation between grade-1 endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) is crucial to determine optimal surgical management. However, discrepancies exist between preoperative diagnosis of AEH and final histology. Our aim was to establish clusters of immunohistochemical markers to distinguish AEH from grade-1 EC. METHODS: We studied 13 immunohistochemical markers (steroid receptors, pro/anti apoptotic proteins, metalloproteinases (MMP) and tissue inhibitor of metalloproteinase (TIMP), and CD44 isoforms) known for their role in endometrial pathology. Using supervised clustering, we determined clusters of co-expressed proteins which contributed the most in differentiating grade-1 EC from AEH. RESULTS: From 42 tissue samples (20 ECs and 22 AEHs), we found 3 clusters of co-expressed proteins: Cluster 1 included 3 proteins (over-expression of MMP-9 and under-expression of estrogen receptor (ER) and progesterone receptor (PR) A in grade-1 EC compared to AEH); cluster 2 showed an MMP-9 over-expression and ER under-expression; cluster 3 showed over-expression of MMP-9 and bcl-2 and under-expression of ER, PR A and CD44-v6 variant. These three clusters together predicted grade-1 EC with a misclassification rate of 8%. CONCLUSION: Supervised clustering of immunohistochemical markers in grade-1 EC and AEH tissue identified proteins acting together and resulted in accurate differentiation between these two histological entities.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Endometrioide/química , Hiperplasia Endometrial/metabolismo , Neoplasias do Endométrio/química , Metaloproteinases da Matriz/análise , Receptores de Esteroides/análise , Inibidores Teciduais de Metaloproteinases/análise , Idoso , Apoptose , Carcinoma Endometrioide/patologia , Diagnóstico Diferencial , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/patologia , Receptor alfa de Estrogênio/análise , Feminino , Humanos , Receptores de Hialuronatos/análise , Imuno-Histoquímica , Antígeno Ki-67/análise , Pessoa de Meia-Idade , Gradação de Tumores , Proteínas Proto-Oncogênicas c-bcl-2/análise , Receptores de Progesterona/análise , Proteína Supressora de Tumor p53/análise
7.
Acta Obstet Gynecol Scand ; 93(3): 261-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24372487

RESUMO

OBJECTIVE: To evaluate ultrasonography and magnetic resonance imaging (MRI) performance in differentiating benign leiomyomas from malignant mesenchymal or mixed tumors (MMT) and smooth muscle tumors of uncertain malignant potential of the uterus (STUMP). DESIGN: Retrospective cohort study. SETTING: University hospital, France. POPULATION: One hundred and eight women who underwent imaging before surgery for uterine mesenchymal tumor (85 with benign leiomyomas and 23 with MMT/STUMP). METHODS: The ultrasonography reports were reviewed. Conventional, perfusion and diffusion MRI were blindly analyzed. Recursive partitioning analysis (RPA) was performed to construct diagnostic flowcharts. MAIN OUTCOME MEASURES: Accuracy of a diagnostic flowchart. RESULTS: At ultrasonography, single tumor, non-myometrial origin, absence of acoustic shadowing, thickened endometrium and ascites were associated with MMT/STUMP (p = 0.001, p < 0.001, p = 0.03, p < 0.0001 and p = 0.03, respectively). For conventional MRI, single tumor, non-myometrial origin, large tumor, poorly defined margins, thickened endometrium, peritoneal implants, intermediate or high signal intensity in T1 or T2 sequences, heterogeneous T1 signal, cystic alteration of the tumor and heterogeneity of the tumor's enhancement were significantly associated with MMT/STUMP. Perfusion weighted imaging and perfusion curve types were not discriminant. For diffusion weighted imaging, a high signal intensity at b = 1000 s/mm² was associated with MMT/STUMP (p < 0.001). RPA resulted in a model that ultimately included age, number of tumors and the aspect of the endometrium (both evaluated by MRI) and that had an area under the curve of 0.95. CONCLUSIONS: Simple criteria, such as single tumor, non-myometrial tumor, abnormal endometrium and age, should question the diagnosis of benign leiomyoma. MRI enhanced the sensitivity of detecting MMT/STUMP.


Assuntos
Leiomioma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Mesenquimoma/diagnóstico por imagem , Tumor de Músculo Liso/diagnóstico por imagem , Neoplasias Uterinas/diagnóstico por imagem , Adulto , Área Sob a Curva , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Humanos , Leiomioma/diagnóstico , Mesenquimoma/patologia , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Tumor de Músculo Liso/patologia , Ultrassonografia , Neoplasias Uterinas/classificação , Neoplasias Uterinas/diagnóstico
8.
Gynecol Oncol ; 130(3): 457-62, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23770577

RESUMO

OBJECTIVE: The aim of this study was to build a model to predict the risk of lymph node metastases (LNM) in women with low- or intermediate-risk endometrial cancer (EC) using histological and immunohistochemical markers. METHODS: Samples were collected from 68 women with low- or intermediate-risk EC. European Society of Medical Oncology (ESMO) risk group, lymphovascular space involvement (LVSI), immunostaining expressions of Estrogen receptor (ER) and Progesteron receptor (PR) were used to build a recursive partitioning model to predict final lymph node status. RESULTS: The number of women with final low- and intermediate risk EC was 34 (50%) each. LVSI was present in 7 women with low-risk (20%) and 28 (80%) with intermediate-risk EC. Nineteen women (28%) had LNM at final histology. A lower immunostaining of ER (p=0.02) and PR (p=0.03) was found in women with LNM compared with those without. Women were correctly classified by the model in 87% of cases; among the 56 women without LNM that were predicted, 48 (86%) had no LNM at final histology. Among the 12 women with LNM predicted, 11 (92%) had LNM at final histology. CONCLUSIONS: Our results show that lymph node status can be predicted with a relatively high accuracy in women with low- or intermediate-risk EC. This can help physicians to better adapt surgical staging and adjuvant therapies.


Assuntos
Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Vasos Sanguíneos/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Metástase Linfática , Vasos Linfáticos/patologia , Gradação de Tumores , Invasividade Neoplásica , Fatores de Risco
9.
Am J Obstet Gynecol ; 202(2): 178.e1-178.e10, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20113693

RESUMO

OBJECTIVE: The aim of this study was to compare carcinomatosis scores, and to determine their relevance to predict resectability, morbidity, and outcome. STUDY DESIGN: From 2005-2008, 61 patients underwent surgery for ovarian cancer. We compared International Federation Gynecology and Obstetrics (FIGO), peritoneal cancer index, Eisenkop, Aletti, Fagotti, and Fagotti-modified scores. RESULTS: There was a strong correlation between the different scores. In predicting resectability, Fagotti-modified and peritoneal cancer index outperformed other scores. We demonstrated a strong association between the occurrence of postoperative complications and Aletti, peritoneal cancer index, and Eisenkop scores (P < .0001). For progression-free survival, we observed significant differences among FIGO, peritoneal cancer index, Eisenkop, Fagotti-modified, and Aletti stages (P < .05). For stage III/IV patients, only Aletti score remains significant to predict resectability. This suggests that complete respectability is more related to the surgical effort than to the extent of the disease. CONCLUSION: Alternative ranking systems provide additional information over FIGO for complete resectability, complications, and survival.


Assuntos
Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/secundário , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , Curva ROC
10.
Pathol Oncol Res ; 25(2): 461-469, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29264761

RESUMO

Considerable heterogeneity exists in outcomes of early endometrial cancer (EC) according to the type but also the histological grading. Our goal was to describe the immunohistochemical profiles of type I EC according to grades and type II EC, to identify groups of interacting proteins using principal component analysis (PCA) and unsupervised clustering. We studied 13 immunohistochemical markers (steroid receptors, pro/anti-apoptotic proteins, metalloproteinases (MMP) and tissue inhibitor of metalloproteinase (TIMP), and CD44 isoforms known for their role in endometrial pathology. Co-expressed proteins associated with the type, grade and outcome of EC were determined by PCA and unsupervised clustering. PCA identified three functional groups of proteins from 43 tissue samples (38 type I and 5 type II EC): the first was characterized by p53 expression; the second by MMPs, bcl-2, PR B and CD44v6; and the third by ER alpha, PR A, TIMP-2 and CD44v3. Unsupervised clustering found two main clusters of proteins, with both type I grade 3 and type II EC exhibiting the same cluster profile. PCA and unsupervised clustering of immunohistochemical markers in EC contribute to a better comprehension and classification of the disease.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias do Endométrio/patologia , Análise por Conglomerados , Feminino , Humanos , Imuno-Histoquímica , Gradação de Tumores
11.
Int J Oncol ; 33(6): 1239-46, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19020757

RESUMO

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play key roles in tumorigenesis, but little is known of their expression according to mucinous or serous type. This study aimed to evaluate the immunohistochemical expression of MMP-2, -7, -9, MT1-MMP, TIMP-1 and -2 in these tumors. A tissue microarray was set up including 99 serous (25 benign, 27 borderline, 47 malignant) and 79 mucinous (25 benign, 44 borderline, 10 malignant) ovarian tumors. Immunostaining results were scored by using the HSCORE and assessed by univariate, unsupervised hierarchical clustering and multidimensional scaling analyses. Epithelial expression of MMP-2, -7, -9, MT1-MMP, TIMP-2, but not TIMP-1, was higher in serous than mucinous tumors. Stromal expression of MMP-7 was higher in serous tumors. Alterations in MT1-MMP, MMP-7 and -9 were found in malignant serous tumors, while benign and borderline tumors shared similar expressions. By unsupervised hierarchical clustering analysis, mucinous and serous tumors were better differentiated by epithelial than stromal MMP and TIMP immunolabelling. By multidimensional scaling analysis, the expressions of MMPs and TIMPs were scattered in serous tumors and homogeneous for mucinous tumors. In conclusion, our results support the differential expression in MMPs and TIMPs of ovarian tumors according to serous or mucinous histology.


Assuntos
Cistadenoma Mucinoso/química , Cistadenoma Seroso/química , Metaloproteinases da Matriz/análise , Neoplasias Ovarianas/química , Inibidor Tecidual de Metaloproteinase-1/análise , Inibidor Tecidual de Metaloproteinase-2/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Cistadenoma Mucinoso/enzimologia , Cistadenoma Mucinoso/patologia , Cistadenoma Seroso/enzimologia , Cistadenoma Seroso/patologia , Feminino , Humanos , Imuno-Histoquímica , Metaloproteinase 14 da Matriz/análise , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 7 da Matriz/análise , Metaloproteinase 9 da Matriz/análise , Pessoa de Meia-Idade , Neoplasias Ovarianas/enzimologia , Neoplasias Ovarianas/patologia , Análise Serial de Tecidos , Adulto Jovem
12.
Am J Obstet Gynecol ; 199(3): 244.e1-7, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18486086

RESUMO

OBJECTIVE: The objective of the study was to study factors influencing the use and accuracy of frozen section diagnosis (FSD) of ovarian tumors. STUDY DESIGN: Surgery was performed in 414 patients with epithelial ovarian tumors between 2001 and 2006. Factors were identified by univariate and multivariate analysis. RESULTS: FSD was requested in 274 patients: 152 benign, 55 borderline, and 67 malignant tumors. Age 50 years or older, tumor size 10 cm or greater, and preoperative evidence of malignancy were associated with FSD request. The sensitivity and specificity of FSD for benign, borderline, and malignant tumors were 97% and 81%, 62% and 96%, and 88% and 99%, respectively. The histologic type (mucinous), tumor size (less than 10 cm), the borderline component (less than 10%), and the pathologist's experience predicted misdiagnosis of borderline tumors. Spread outside the ovary was the only significant predictor of accurate FSD of malignant tumors. CONCLUSION: FSD is less accurate for borderline than benign and malignant ovarian tumors. The pathologist's experience is a major determinant of diagnostic accuracy.


Assuntos
Secções Congeladas , Neoplasias Ovarianas/patologia , Epitélio/patologia , Feminino , Humanos , Período Intraoperatório , Funções Verossimilhança , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Ovarianas/cirurgia , Estudos Retrospectivos , Sensibilidade e Especificidade
13.
J Reprod Immunol ; 70(1-2): 151-62, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16378643

RESUMO

Endometriosis is defined as the presence of endometrial glands and stroma outside the uterus. Apoptosis, a physiological process by which multicellular organisms eliminate superfluous cells, is altered in tumor tissue. Here we studied the expression of the apoptosis-related proteins p53, bcl-2, bax, p21 and fas in proliferative (n=9) and secretory (n=9) endometrium, and in peritoneal (n=11), ovarian (n=20) and colorectal (n=20) endometriosis, by qualitative and semi-quantitative immunohistochemical methods using the percentage of positive cells and HSCORE analysis. In endometrium, p53, p21 and fas expression was low, whereas bax and bcl-2 expression was elevated. Using HSCORE analysis, only bcl-2 expression varied during the menstrual cycle (48.9+/-34.2% in the proliferative phase, 11.5+/-24.7% in the secretory phase, p=0.01). Using HSCORE analysis, p53 expression was higher in ovarian endometriosis than in peritoneal (p<0.0001) and colorectal endometriosis (p=0.03). P21 expression was higher in ovarian endometriosis than in peritoneal (p=0.01) and colorectal endometriosis (p=0.01). Bcl-2 expression was lower in ovarian endometriosis than in peritoneal (p=0.0002) and colorectal endometriosis (p<0.0001). Fas expression was higher in peritoneal endometriosis than in ovarian (p=0.02) and colorectal endometriosis (p=0.008). In conclusion, these results confirm the involvement of apoptosis in the pathogenesis of endometriosis. Moreover, expression of apoptosis-related proteins varies according to the location of endometriosis suggesting the involvement of different apoptotic pathways.


Assuntos
Proteínas Reguladoras de Apoptose/biossíntese , Apoptose/fisiologia , Doenças do Colo/metabolismo , Endometriose/metabolismo , Proteínas Inibidoras de Apoptose/biossíntese , Doenças Ovarianas/metabolismo , Doenças Peritoneais/metabolismo , Doenças Retais/metabolismo , Doenças do Colo/patologia , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Endometriose/patologia , Feminino , Humanos , Imuno-Histoquímica , Doenças Ovarianas/patologia , Doenças Peritoneais/patologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Doenças Retais/patologia , Proteína Supressora de Tumor p53/biossíntese , Proteína X Associada a bcl-2/biossíntese , Receptor fas/biossíntese
14.
Biochim Biophys Acta ; 1688(3): 250-6, 2004 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-15062876

RESUMO

Most gastrointestinal stromal tumors (GISTs) contain activating mutations of the proto-oncogene c-kit. The GNNK- isoform of c-kit has a greater oncogenic potential than the GNNK+ isoform. We studied tumors from 29 patients with GIST, 19 of whom had c-kit mutations, and compared them to normal cells and HMC-1 mast cell line. c-kit transcripts were quantified by real-time PCR. The ratios of GNNK-/+ isoforms and of wild-type/mutant alleles were determined by RT-PCR and fluorometric quantification. On average, GISTs contained 1.9 times more c-kit transcripts than the HMC-1 cell line and GISTs with c-kit mutations contained 2.8 times more c-kit transcripts than those without (P=0.003). The median GNNK-/+ isoform ratios in GISTs with and without c-kit mutations were 4.4 and 4.1, respectively, and there was no difference in the GNNK-/+ ratios between the GISTs and the control samples. Both mutant and wild-type alleles of c-kit were expressed in similar amounts in 13/15 mutant GISTs. The oncogenic effects of KIT in GISTs are not related to the higher expression level of the GNNK- isoform. The high expression level of both mutated and wild-type allele transcripts of c-kit suggests that interactions between spontaneously activated and normal c-kit receptors are important in GIST tumorigenesis.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Mutação/genética , Proteínas Proto-Oncogênicas c-kit/genética , Neoplasias Gástricas/genética , Adulto , Idoso , Sequência de Bases , Primers do DNA , Feminino , Humanos , Imuno-Histoquímica , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Proto-Oncogene Mas , RNA Mensageiro/genética , Neoplasias Gástricas/patologia , Células Estromais/patologia , Transcrição Gênica
15.
J Reprod Immunol ; 65(1): 55-63, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15694967

RESUMO

BACKGROUND: Endometriosis is defined by the presence of endometrium outside the uterus. Changes in the expression of the proto-oncogene c-kit are associated with aggressive behaviour of both benign and malignant tumours, but there are few data on its c-kit expression in endometriosis. Here we examined c-kit expression in endometrium and endometriotic tissue. METHODS: Immunohistochemistry was used for qualitative and semi-quantitative (mean+/-S.D. positive cells) analysis of c-kit expression in endometrium from women with (n=9) and without endometriosis (n=18), and in peritoneal (n=20), ovarian (n=20) and colorectal endometriosis (n=20). RESULTS: Semi-quantitative c-kit expression was higher in endometrial glandular cells from women with endometriosis than from women without endometriosis (15.0+/-14.6% versus 3.9+/-7.4%, p=0.01). No difference in c-kit expression was found in qualitative analysis and according to the phase of the menstrual cycle. C-kit expression values in peritoneal, ovarian and colorectal endometriosis were 2.0+/-3.8%, 2.0+/-4.1% and 21.7+/-18.4%, respectively. Qualitative and semi-quantitative c-kit expression was higher in colorectal endometriosis than in peritoneal and ovarian endometriosis (p<0.001); no difference was found between ovarian and peritoneal endometriosis. No c-kit expression was detected in stromal cells of either endometrium or endometriotic tissue. CONCLUSION: These results suggest that the c-kit/stem cell factor axis is involved in the pathogenesis of endometriosis. Strong c-kit protein expression was associated with invasive endometriotic lesions.


Assuntos
Endometriose/metabolismo , Endométrio/metabolismo , Regulação da Expressão Gênica , Proteínas Proto-Oncogênicas c-kit/biossíntese , Adulto , Colo/metabolismo , Colo/patologia , Endometriose/patologia , Endométrio/patologia , Feminino , Humanos , Ovário/metabolismo , Ovário/patologia , Peritônio/metabolismo , Peritônio/patologia , Proto-Oncogene Mas
16.
J Reprod Med ; 50(3): 222-4, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15841939

RESUMO

BACKGROUND: Bilateral tubal pregnancy is very rare and usually follows ovulation stimulation. CASE: A 36-year-old woman with acute pelvic pain underwent emergency laparoscopy for suspected left ruptured tubal pregnancy. Bilateral hematosalpinx with a ruptured left tubal pregnancy and active bleeding from the right fallopian tube was noted during surgery, and bilateral salpingectomy was performed by laparoscopy. Pathologic examination of the left tube confirmed the presence of conception products and trophoblastic tissue. The right salpingectomy specimen contained some trophoblastic tissue resembling an earlier tubal pregnancy encased in a cyst. CONCLUSION: This was a rare case of spontaneous bilateral tubal pregnancy after conception at different times. The explanation of the presentation is uncertain. Laparoscopy remains the cornerstone of diagnosis and treatment in the majority of women with a tubal pregnancy; this is especially true in complex cases, such as bilateral tubal pregnancy.


Assuntos
Fertilização , Gravidez Tubária/patologia , Adulto , Feminino , Lateralidade Funcional , Hemoperitônio/etiologia , Humanos , Laparoscopia , Dor Pélvica/etiologia , Gravidez , Gravidez Tubária/cirurgia
17.
Anticancer Res ; 35(12): 6799-804, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26637899

RESUMO

AIM: To compare the risk of developing endometrial carcinoma (EC) in young women with atypical endometrial hyperplasia (AEH) undergoing fertility-sparing management compared to women treated by primary hysterectomy. PATIENTS AND METHODS: In this multicentric retrospective study, 111 patients with a diagnosis of AEH by endometrial biopsy were included. EC incidence was compared in two groups: 32 patients treated with fertility-sparing management and 79 older patients treated with primary hysterectomy. RESULTS: The rates of EC diagnosed by pathology of hysterectomy specimens were comparable between the groups. The probability of developing EC at 12, 24 and 36 months were 14%, 21% and 26%, respectively, in patients managed conservatively, and 29%, 37% and 37%, respectively, in patients treated with primary hysterectomy. CONCLUSION: Fertility-sparing management of AEH does not increase the risk of diagnosing EC from the hysterectomy specimen.


Assuntos
Hiperplasia Endometrial/terapia , Neoplasias do Endométrio/prevenção & controle , Preservação da Fertilidade/métodos , Histerectomia/métodos , Adulto , Progressão da Doença , Hiperplasia Endometrial/diagnóstico , Neoplasias do Endométrio/patologia , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
18.
Virchows Arch ; 445(6): 603-9, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15452706

RESUMO

Endometriosis is subsequent to the ability of endometrial glands to invade normal tissues. Matrix metalloproteinases (MMPs)--enzymes that mediate normal tissue turnover, including endometrial breakdown during menstruation-appear to be involved in this invasive process. Here, we examined the immunohistochemical expression of MMP-2, MMP-3, MMP-11, tissue inhibitor metalloproteinase (TIMP)-1 and TIMP-2 in endometrium from women with (n=9) or without endometriosis (n=18) in comparison with peritoneal (n=20), ovarian (n=20) and colorectal endometriosis (n=20). Women with endometriosis showed decreased endometrial MMP-2 expression compared with women without endometriosis (mean+/-SD positive cells: 24.3+/-28.3% and 69.3+/-12.1%), together with loss of MMP-3 expression (0 versus 17.5%+/-20.2). MMP-11, TIMP-1 and TIMP-2 expression was similar in the two groups. Endometrial MMP-2, -3 and -11 expression and TIMP-1 and -2 expression were similar in women with endometriosis and in those with peritoneal endometriosis. MMP-2, -3 and -11 expression was higher in colorectal endometriosis than in ovarian and peritoneal endometriosis. TIMP-2 expression was lower in colorectal endometriosis (P=0.0002) and ovarian endometriotic cysts (P=0.003) than in peritoneal endometriosis. TIMP-1 expression did not vary according to the location of endometriotic lesions. These results suggest that MMP-2 and -3 and TIMP-2 may be involved in the pathogenesis of endometriosis. Interestingly, MMP-2 and -3 overexpression was related to the infiltrative nature of endometriotic lesions, with possible sequential expression from peritoneal to colorectal endometriosis.


Assuntos
Endometriose/enzimologia , Endométrio/enzimologia , Enteropatias/enzimologia , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 3 da Matriz/análise , Metaloendopeptidases/análise , Doenças Ovarianas/enzimologia , Doenças Peritoneais/enzimologia , Inibidor Tecidual de Metaloproteinase-1/análise , Inibidor Tecidual de Metaloproteinase-2/análise , Feminino , Humanos , Imuno-Histoquímica , Metaloproteinase 11 da Matriz
19.
J Reprod Med ; 49(7): 578-81, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15305834

RESUMO

BACKGROUND: Epithelioid angiomyolipoma is a recently recognized pathologic entity. The occurrence of epithelioid angiomyolipoma in thefemale genital tract is rare. CASE: A case of uterine epithelioid angiomyolipoma occurred in a young woman without tuberous sclerosis and underwent an early recurrence with lymph node metastasis. CONCLUSION: Uterine epithelioid angiomyolipoma should be considered in young women with a tumor exhibiting high intratumoral linear vascularity and aneurysmal dilation.


Assuntos
Angiomiolipoma/patologia , Neoplasias Uterinas/patologia , Adolescente , Angiomiolipoma/diagnóstico por imagem , Angiomiolipoma/cirurgia , Células Epitelioides/patologia , Feminino , Humanos , Laparoscopia , Metástase Linfática , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/cirurgia , Reoperação , Ultrassonografia , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/cirurgia
20.
BMJ Case Rep ; 20142014 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-24671316

RESUMO

Vulvar endometriosis can occur after surgery or trauma and cause dyspareunia. A 30-year-old woman presented with orificial dyspareunia lasting for 5 months. Her history was marked by a vaginal birth without perineal injury and the removal of a cyst from the left Bartholin's gland. On examination, we observed a selectively painful, superficial and retractile lesion, 5 mm in diameter at the junction of the hymen at some distance from the bartholinitis scar. Endometriosis was suspected due to the exacerbation of pain during menses. The surgery consisted of excision of the hymenal area of the painful lesion. Pathological examination confirmed the presence of endometrial tissue. The painful symptoms resolved and no additional treatment was administered. Any vulvar lesion, regardless of its appearance and location, can be related to endometriosis. Surgical resection is recommended to relieve the symptoms and provide histological proof.


Assuntos
Dispareunia/etiologia , Endometriose/patologia , Hímen/patologia , Doenças da Vulva/patologia , Adulto , Endometriose/complicações , Endometriose/cirurgia , Feminino , Humanos , Hímen/cirurgia , Doenças da Vulva/complicações , Doenças da Vulva/cirurgia
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