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1.
Pathol Oncol Res ; 25(2): 461-469, 2019 Apr.
Article En | MEDLINE | ID: mdl-29264761

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.


Biomarkers, Tumor/analysis , Endometrial Neoplasms/pathology , Cluster Analysis , Female , Humans , Immunohistochemistry , Neoplasm Grading
2.
Ann Surg Oncol ; 23(1): 171-7, 2016 Jan.
Article En | MEDLINE | ID: mdl-25952272

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.


Endometrial Neoplasms/pathology , Lymph Node Excision , Neoplasm Recurrence, Local/epidemiology , Tumor Burden , Aged , Endometrial Neoplasms/surgery , Female , Follow-Up Studies , France/epidemiology , Humans , Incidence , Lymphatic Metastasis , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Retrospective Studies , Risk Factors , Survival Rate
3.
Anticancer Res ; 35(12): 6799-804, 2015 Dec.
Article En | MEDLINE | ID: mdl-26637899

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.


Endometrial Hyperplasia/therapy , Endometrial Neoplasms/prevention & control , Fertility Preservation/methods , Hysterectomy/methods , Adult , Disease Progression , Endometrial Hyperplasia/diagnosis , Endometrial Neoplasms/pathology , Female , Humans , Incidence , Middle Aged , Retrospective Studies , Risk Factors , Young Adult
4.
Ann Surg Oncol ; 22(13): 4224-32, 2015 Dec.
Article En | MEDLINE | ID: mdl-25869227

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.


Endometrial Neoplasms/pathology , Models, Theoretical , Myometrium/pathology , Neoplasm Recurrence, Local/pathology , Adult , Aged , Aged, 80 and over , Cohort Studies , Endometrial Neoplasms/mortality , Endometrial Neoplasms/surgery , Female , Follow-Up Studies , Humans , Lymph Node Excision , Lymphatic Metastasis , Middle Aged , Myometrium/surgery , Neoplasm Invasiveness , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Nomograms , Predictive Value of Tests , Prognosis , ROC Curve , Risk Assessment , Survival Rate , Tumor Burden
6.
Gynecol Oncol ; 136(1): 112-20, 2015 Jan.
Article En | MEDLINE | ID: mdl-25449309

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.


Biomarkers, Tumor/metabolism , Neoplasms, Glandular and Epithelial/drug therapy , Neoplasms, Glandular and Epithelial/metabolism , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/administration & dosage , Carcinoma, Ovarian Epithelial , Chemotherapy, Adjuvant , DNA-Binding Proteins/metabolism , Drug Resistance, Neoplasm , Endonucleases/metabolism , Female , Humans , Hyaluronan Receptors/metabolism , Interleukin-6/metabolism , Interleukin-8/metabolism , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Neoplasms, Glandular and Epithelial/pathology , Neoplasms, Glandular and Epithelial/surgery , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Paclitaxel/administration & dosage
7.
Gynecol Endocrinol ; 31(4): 282-5, 2015 Apr.
Article En | MEDLINE | ID: mdl-25495249

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.


Endometrial Hyperplasia/diagnosis , Endometrium/metabolism , Biomarkers/metabolism , Cluster Analysis , Diagnosis, Differential , Down-Regulation , Endometrial Hyperplasia/metabolism , Endometrial Hyperplasia/pathology , Endometrium/enzymology , Endometrium/pathology , Estrogen Receptor alpha/metabolism , Female , Humans , Immunohistochemistry , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 7/metabolism , Middle Aged , Predictive Value of Tests , Receptors, Progesterone/metabolism , Supervised Machine Learning , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tissue Inhibitor of Metalloproteinase-2/metabolism , Up-Regulation
8.
Am J Obstet Gynecol ; 212(1): 56.e1-7, 2015 Jan.
Article En | MEDLINE | ID: mdl-24983678

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.


Carcinoma, Endometrioid/secondary , Endometrial Neoplasms/pathology , Lymphatic Metastasis , Nomograms , Female , Humans , Middle Aged , Neoplasm Staging , Prospective Studies
9.
Anticancer Res ; 34(10): 5671-6, 2014 Oct.
Article En | MEDLINE | ID: mdl-25275072

AIM: To identify predictive factors of endometrial cancer in patients with atypical endometrial hyperplasia (AEH). PATIENTS AND METHODS: This was a retrospective cohort study of 79 patients diagnosed with AEH. Clinicopathological characteristics of patients and final histology on hysterectomy were reviewed and univariate and multivariate analyses were performed. RESULTS: Nineteen cases of endometrial cancer (24%) were diagnosed at final histology. Most patients had IA (n=15, 79%) grade 1 (n=15, 79%) cancer, but two had FIGO stage IIIC (10.5%). The predictive factors of endometrial cancer on final histology in univariate analysis were: hysteroscopic sampling, older age, post-menopausal status, suspicion of cancer on hysteroscopy and suspicion of cancer at histology. In multivariable analysis, the only predictive factors of endometrial cancer were older age and the suspicion of cancer on hysteroscopy. CONCLUSION: In patients with AEH on biopsy, our results showed that hysteroscopy could be performed both to assess macroscopic features of malignancy and to orient biopsy.


Endometrial Hyperplasia/complications , Endometrial Hyperplasia/pathology , Endometrial Neoplasms/epidemiology , Endometrial Neoplasms/etiology , Aged , Biopsy , Endometrial Neoplasms/diagnosis , Endometrium/pathology , Female , Humans , Incidence , Menopause , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prognosis , Retrospective Studies , Risk Factors
10.
BMJ Case Rep ; 20142014 Mar 26.
Article En | MEDLINE | ID: mdl-24671316

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.


Dyspareunia/etiology , Endometriosis/pathology , Hymen/pathology , Vulvar Diseases/pathology , Adult , Endometriosis/complications , Endometriosis/surgery , Female , Humans , Hymen/surgery , Vulvar Diseases/complications , Vulvar Diseases/surgery
11.
Gynecol Oncol ; 133(2): 205-10, 2014 May.
Article En | MEDLINE | ID: mdl-24556060

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.


Biomarkers, Tumor/analysis , Carcinoma, Endometrioid/chemistry , Endometrial Hyperplasia/metabolism , Endometrial Neoplasms/chemistry , Matrix Metalloproteinases/analysis , Receptors, Steroid/analysis , Tissue Inhibitor of Metalloproteinases/analysis , Aged , Apoptosis , Carcinoma, Endometrioid/pathology , Diagnosis, Differential , Endometrial Hyperplasia/pathology , Endometrial Neoplasms/pathology , Estrogen Receptor alpha/analysis , Female , Humans , Hyaluronan Receptors/analysis , Immunohistochemistry , Ki-67 Antigen/analysis , Middle Aged , Neoplasm Grading , Proto-Oncogene Proteins c-bcl-2/analysis , Receptors, Progesterone/analysis , Tumor Suppressor Protein p53/analysis
12.
Acta Obstet Gynecol Scand ; 93(3): 261-8, 2014 Mar.
Article En | MEDLINE | ID: mdl-24372487

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.


Leiomyoma/diagnostic imaging , Magnetic Resonance Imaging/methods , Mesenchymoma/diagnostic imaging , Smooth Muscle Tumor/diagnostic imaging , Uterine Neoplasms/diagnostic imaging , Adult , Area Under Curve , Cohort Studies , Diagnosis, Differential , Female , Humans , Leiomyoma/diagnosis , Mesenchymoma/pathology , Middle Aged , Multivariate Analysis , Retrospective Studies , Smooth Muscle Tumor/pathology , Ultrasonography , Uterine Neoplasms/classification , Uterine Neoplasms/diagnosis
13.
Gynecol Oncol ; 130(3): 457-62, 2013 Sep.
Article En | MEDLINE | ID: mdl-23770577

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.


Endometrial Neoplasms/metabolism , Endometrial Neoplasms/pathology , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Blood Vessels/pathology , Endometrial Neoplasms/surgery , Female , Humans , Lymphatic Metastasis , Lymphatic Vessels/pathology , Neoplasm Grading , Neoplasm Invasiveness , Risk Factors
14.
Oncol Rep ; 27(4): 1049-57, 2012 Apr.
Article En | MEDLINE | ID: mdl-22200690

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in tumor invasion, but their prognostic significance is still under discussion. We set out to analyze the epithelial and stromal expression of MMP-2, MMP-7, MMP-9, MT1-MMP, TIMP-1 and TIMP-2 in advanced epithelial ovarian cancers and to assess their prognostic value. A tissue microarray of malignant ovarian tumors from 69 patients was constructed. Immunostaining results were scored using the HSCORE and assessed by univariate analysis with Bonferroni correction and classical multidimensional scaling (CMDS). Kaplan-Meier survival curves calculated with regard to patient and tumor characteristics were compared by the log-rank test. Patients treated by primary surgery (n=43) had a higher tumor size and a trend toward higher epithelial MMP and TIMP expression than those treated by interval surgery (n=26). Optimal cytoreduction (residue ≤ 1 cm) was obtained in 27 and 18 patients, respectively. Clinical and histological characteristics were not different in patients with optimal cytoreduction and those with suboptimal cytoreduction. The expression of epithelial MMP-9 (P=0.002) and TIMP-2 (P=0.026) were higher in the latter group. CMDS failed to demonstrate any influence of MMP and TIMP expression with regard to cytoreduction outcome. MMP and TIMP expression did not influence survival. Their prognostic values were outweighed by histological type, lymph node involvement and cytoreduction. Standard statistical analysis adjusted after Bonferroni correction and CMDS reduced the relevance of MMPs and TIMPs in the prognosis of patients with advanced ovarian cancer.


Biomarkers, Tumor/analysis , Matrix Metalloproteinase 14/analysis , Matrix Metalloproteinase 2/analysis , Matrix Metalloproteinase 7/analysis , Matrix Metalloproteinase 9/analysis , Neoplasms, Glandular and Epithelial/chemistry , Neoplasms, Glandular and Epithelial/surgery , Ovarian Neoplasms/chemistry , Ovarian Neoplasms/surgery , Tissue Inhibitor of Metalloproteinase-1/analysis , Tissue Inhibitor of Metalloproteinase-2/analysis , Adult , Aged , Aged, 80 and over , Carcinoma, Ovarian Epithelial , Chemotherapy, Adjuvant , Chi-Square Distribution , Disease-Free Survival , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Middle Aged , Neoadjuvant Therapy , Neoplasm Grading , Neoplasms, Glandular and Epithelial/mortality , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Ovariectomy , Paris , Principal Component Analysis , Risk Assessment , Risk Factors , Time Factors , Tissue Array Analysis , Treatment Outcome
15.
Am J Obstet Gynecol ; 202(2): 178.e1-178.e10, 2010 Feb.
Article En | MEDLINE | ID: mdl-20113693

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.


Ovarian Neoplasms/surgery , Peritoneal Neoplasms/secondary , Female , Humans , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Prognosis , ROC Curve
16.
Cancer ; 116(4): 799-804, 2010 Feb 15.
Article En | MEDLINE | ID: mdl-20041486

BACKGROUND: The objective of this study was to describe the characteristics and survival outcomes of patients with breast cancer who had ovarian metastases. METHODS: Data from 29 women who underwent surgery were reviewed retrospectively (from 1998 to 2007). Patient characteristics, tumor characteristics, and treatment data were collected. Pelvic extent of disease was documented using a system analogous to the International Federation of Gynecology and Obstetrics classification for ovarian cancer. Global survival, disease-free intervals, and the distribution to other metastatic sites over time were studied. Outcomes were compared between the group who underwent macroscopic resection of lesions and the group who did not undergo resection. RESULTS: The data indicated a predominance of premenopausal and hormone receptor-positive status and a greater prevalence of lobular infiltrating carcinoma, bilateral breast cancer, and predisposing genetic factors compared with the global population with breast cancer. Ovarian disease was diagnosed at a median of 5 years after breast cancer. Seventy-five percent of patients were asymptomatic, and advanced-stage pelvic extent or extra-abdominal metastases were observed in 41.5% of patients. The median survival was 3 years, and the median follow-up was 2 years. Survival improved significantly when optimal debulking surgery was performed. CONCLUSIONS: Breast cancers may be associated with ovarian metastases. The current results indicated that surgical resection tends to increase survival, which may be long; however, larger series would be needed to confirm other prognostic factors. The high rates of hormone receptor-positive tumors and premenopausal patients led the authors to suggest that the surgical option should consist of at least bilateral oophorectomy, even when the contralateral ovary appears to be normal.


Breast Neoplasms/pathology , Ovarian Neoplasms/secondary , Adult , Aged , Breast Neoplasms/therapy , Disease-Free Survival , Female , Humans , Middle Aged , Neoplasm Metastasis , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Retrospective Studies , Time Factors
17.
Cases J ; 2: 7515, 2009 May 18.
Article En | MEDLINE | ID: mdl-19829987

INTRODUCTION: Uterine adenosarcoma is a rarely observed polypoid tumor with a mixed benign epithelial element and malignant stromal component. The treatment is total hysterectomy with bilateral salpingo-oophorectomy. It could be difficult to diagnose and associated to lymphovascular invasion. CASE PRESENTATION: A 45-year-old caucasian uniparous woman presented with uterine bleeding. She had several surgical procedures and pathology of removed recurrent polyps showed no malignancy. Finally, a total abdominal hysterectomy was performed because of atypical cells and suspected uterine adenosarcoma. The hysterectomy specimen confirmed the presence of uterine adenosarcoma associated with lymphatic and vascular tumor emboli. Surgery was completed with a second bilateral salpingo-oophorectomy and pelvic lymphadenectomy. CONCLUSION: In our report, we present a case of uterine adenosarcoma which was diagnosed after multiple surgical procedures and associated to lymphovascular emboli known to have a significant impact on overall survival and distant metastasis-free survival.

18.
Int J Oncol ; 33(6): 1239-46, 2008 Dec.
Article En | MEDLINE | ID: mdl-19020757

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.


Cystadenoma, Mucinous/chemistry , Cystadenoma, Serous/chemistry , Matrix Metalloproteinases/analysis , Ovarian Neoplasms/chemistry , Tissue Inhibitor of Metalloproteinase-1/analysis , Tissue Inhibitor of Metalloproteinase-2/analysis , Adolescent , Adult , Aged , Aged, 80 and over , Cluster Analysis , Cystadenoma, Mucinous/enzymology , Cystadenoma, Mucinous/pathology , Cystadenoma, Serous/enzymology , Cystadenoma, Serous/pathology , Female , Humans , Immunohistochemistry , Matrix Metalloproteinase 14/analysis , Matrix Metalloproteinase 2/analysis , Matrix Metalloproteinase 7/analysis , Matrix Metalloproteinase 9/analysis , Middle Aged , Ovarian Neoplasms/enzymology , Ovarian Neoplasms/pathology , Tissue Array Analysis , Young Adult
19.
Am J Obstet Gynecol ; 199(3): 244.e1-7, 2008 Sep.
Article En | MEDLINE | ID: mdl-18486086

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.


Frozen Sections , Ovarian Neoplasms/pathology , Epithelium/pathology , Female , Humans , Intraoperative Period , Likelihood Functions , Middle Aged , Multivariate Analysis , Ovarian Neoplasms/surgery , Retrospective Studies , Sensitivity and Specificity
20.
J Comput Assist Tomogr ; 31(2): 236-42, 2007.
Article En | MEDLINE | ID: mdl-17414760

PURPOSE: The purpose of this study was to assess the accuracy of magnetic resonance imaging (MRI), particularly, dynamic MRI, in distinguishing ovarian fibromas from subserous uterine leiomyomas. MATERIAL AND METHODS: Fifteen ovarian fibromas and 15 subserous uterine leiomyomas were retrospectively reviewed. All MR examinations included dynamic contrast-enhanced (DCE) sequences. Morphological criteria (size, T1 and T2 signals, ovarian tissue, associated uterine leiomyoma, and pelvic fluid), arterial vessels, time-intensity curves (maximal enhancement and signal intensity at 30, 60, and 90 seconds), and signal intensity on delayed T1-weighted images were compared between the 2 groups. RESULTS: No significant difference in morphological criteria was noted between the 2 types of masses. Visualization of arterial vessels was more frequent in uterine leiomyomas than in ovarian fibromas (P= 0.002). The DCE MR enhancement rate was higher for uterine leiomyomas than for ovarian fibromas in terms of both maximal enhancement (P < 0.001) and enhancement rate at 30 (P = 0.009), 60 (P = 0.007), and 90 seconds (P = 0.0009). On delayed T1 postcontrast sequence, no statistical difference exists between signal intensity of ovarian fibromas and uterine leiomyomas. CONCLUSION: Our findings suggest that DCE MRI can distinguish ovarian fibromas from uterine leiomyomas and should be used if sonography fails to show the origin of a pelvic mass.


Fibroma/diagnosis , Image Enhancement/methods , Leiomyoma/diagnosis , Magnetic Resonance Imaging/methods , Ovarian Neoplasms/diagnosis , Uterine Neoplasms/diagnosis , Adolescent , Adult , Aged , Contrast Media/administration & dosage , Diagnosis, Differential , Female , Humans , Longitudinal Studies , Middle Aged , Observer Variation , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies
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