International Journal of Gynecologic Cancer最新文献

{"title":"Prognostic Significance of Cytokeratin 19 and Squamous Cell Cancer Antigen in Histologically Negative Sentinel Lymph Nodes of Cervical Squamous Cell Carcinoma.","authors":"Jie Ren, Zun-Lun Zhou, Shu Xu, Ying-Jie Yang","doi":"10.1097/IGC.0000000000000813","DOIUrl":"10.1097/IGC.0000000000000813","url":null,"abstract":"<p><strong>Objective: </strong>The aim of the study was to evaluate the prognostic value of positive cytokeratin 19 (CK19) and squamous cell cancer antigen (SCCAg) expression in histologically negative sentinel lymph nodes after surgery for cervical squamous cell carcinoma.</p><p><strong>Methods: </strong>Immunohistochemistry was performed to detect the expression of CK19 and SCCAg using polyclonal antibody on 149 pair of formalin-fixed, paraffin-embedded cervical squamous cell carcinoma and histologically negative sentinel lymph node tissue samples, and results were compared with data from the prospectively registry of cervical squamous cell carcinoma by univariate and multivariate logistic regression model focusing specifically on recurrence. The survival was assessed by the Kaplan-Meier method and proportional hazards model.</p><p><strong>Results: </strong>Cytokeratin 19 and SCCAg expression in histologically negative sentinel lymph nodes were documented in 15.4% (n = 23) and 20.8% (n = 31) patients and were associated with a higher incidence of tumor progression and poorer disease-free survival (DFS, P < 0.05). Multivariate logistic regression analysis demonstrated that CK19 (P = 0.001) and SCCAg (P = 0.001) expression in histologically negative sentinel lymph nodes, International Federation of Gynecology and Obstetrics staging (P = 0.000), and cervical stroma infiltration depth (P = 0.005) were independent predictive factors for recurrence. The proportional hazards model identified CK19 (P = 0.001) and SCCAg (P = 0.005) expression in histologically negative sentinel lymph nodes, International Federation of Gynecology and Obstetrics staging (P = 0.003), and cervical stroma infiltration depth (P = 0.005), as independently related to DFS. Using subgroup analysis, we found that the CK19+/SCCAg + subgroup has the poorest prognosis, whereas the CK19-/SCCAg - subgroup has the best prognosis (P = 0.000).</p><p><strong>Conclusions: </strong>Immunohistochemical assessment of both CK19 and SCCAg status in histologically negative sentinel lymph nodes may be a valuable approach for predicting recurrence and survival after curative surgery for cervical squamous cell carcinoma.</p>","PeriodicalId":13983,"journal":{"name":"International Journal of Gynecologic Cancer","volume":"58 1","pages":"1679-1685"},"PeriodicalIF":0.0,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80239658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Oncologic and Reproductive Outcomes in Young Women With Early Endometrial Cancer Conservatively Treated: A Prospective Study and Literature Update.","authors":"Giuseppe Laurelli, Francesca Falcone, Maria Stella Gallo, Felice Scala, Simona Losito, Vincenza Granata, Marco Cascella, Stefano Greggi","doi":"10.1097/IGC.0000000000000825","DOIUrl":"10.1097/IGC.0000000000000825","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to analyze the long-term oncologic and reproductive outcomes in endometrial cancer (EC) in young patients conservatively treated by combined hysteroscopic resection (HR) and levonorgestrel intrauterine device (LNG-IUD).</p><p><strong>Methods: </strong>Twenty-one patients (age ≤ 40 years; Stage IA, G1-2 endometrioid EC), wishing to preserve their fertility, were enrolled into this prospective study. The HR was used to resect (1) the tumor lesion, (2) the endometrium adjacent to the tumor, and (3) the myometrium underlying the tumor. Hormonal therapy consisted of LNG-IUD (52 mg) for at least 6 months.</p><p><strong>Results: </strong>The median follow-up time is 85 months (range, 30-114). After 3 months from the progestin start date, 18 patients (85.7%) showed a complete regression (CR), 2 (9.5%) showed persistent disease, whereas 1 patient (4.8%) presented with progressive disease and underwent definitive surgery (Stage IA, G3 endometrioid). At 6 months, 1 of the 2 persistences underwent definitive surgery (Stage IA, G1 endometrioid), whereas the other was successfully re-treated. Two recurrences (10.5%) were observed, both involving the endometrium and synchronous ovarian cancer (OC) (atypical hyperplasia and Stage IIB G1 endometrioid OC; Stage IA endometrioid G1 EC, and Stage IA G1 endometrioid OC). The median duration of complete response was 85 months (range, 8-117). Sixty-three percent of complete responders attempted to conceive with 92% and 83% pregnancy and live birth rates, respectively. To date, all patients are alive and have no evidence of disease.</p><p><strong>Conclusions: </strong>After a long follow-up, combined HR and LNG-IUD would seem to improve the efficacy of progestin alone. High pregnancy and live birth rates were observed in women attempting to conceive. This approach is still experimental and should be offered only in the framework of scientific protocols conducted in cancer centers.</p>","PeriodicalId":13983,"journal":{"name":"International Journal of Gynecologic Cancer","volume":"14 1","pages":"1650-1657"},"PeriodicalIF":0.0,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87152950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Leukocyte Antigen-DR Expression is Significantly Related to an Increased Disease-Free and Disease-Specific Survival in Patients With Cervical Adenocarcinoma.","authors":"Sanne Samuels, Vivian M Spaans, Michelle Osse, Lex A W Peters, Gemma G Kenter, Gertjan J Fleuren, Ekaterina S Jordanova","doi":"10.1097/IGC.0000000000000783","DOIUrl":"10.1097/IGC.0000000000000783","url":null,"abstract":"<p><strong>Objectives: </strong>Human leukocyte antigen (HLA) class II antigens are expressed on antigen-presenting cells, that is, macrophages, dendritic cells, and B lymphocytes. Under the influence of IFN-γ, HLA class II molecules can also be expressed on T lymphocytes, epithelial and endothelial cells. In addition, HLA class II antigens can be expressed in a variety of malignancies; however, the link with prognosis and ultimately patient survival is controversial.</p><p><strong>Methods: </strong>The pattern of HLA-DRA expression in cervical carcinoma was studied using immunohistochemistry. In total, 124 cervical carcinomas were examined, of which 60 (48.4%) were squamous cell carcinomas and 64 (51.6%) were adenocarcinomas.</p><p><strong>Results: </strong>In squamous cell carcinoma, HLA-DRA was expressed in 41 (68.3%) of 60 tumors, whereas in adenocarcinoma, HLA-DRA was expressed in 60 (93.8%) of 64 tumors (P < 0.001). In adenocarcinoma, HLA-DRA expression was associated with an increased disease-free survival (211.0 ± 13.0 vs 53.3 ± 30.5 months; P = 0.004) and disease-specific survival (226.45 ± 11.5 vs 75.8 ± 27.6 months; P = 0.002).</p><p><strong>Conclusions: </strong>Upregulation of HLA-DRA is significantly related to an increased disease-free and disease-specific survival in cervical adenocarcinoma. These data warrant further analysis of the functional role of HLA-DRA in these tumors.</p>","PeriodicalId":13983,"journal":{"name":"International Journal of Gynecologic Cancer","volume":"29 1","pages":"1503-1509"},"PeriodicalIF":0.0,"publicationDate":"2016-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85556344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter From Editor-October 2016.","authors":"Uziel Beller","doi":"10.1097/IGC.0000000000000847","DOIUrl":"10.1097/IGC.0000000000000847","url":null,"abstract":"","PeriodicalId":13983,"journal":{"name":"International Journal of Gynecologic Cancer","volume":"13 1","pages":"1365"},"PeriodicalIF":0.0,"publicationDate":"2016-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83674935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L1 Cell Adhesion Molecule as a Predictor of Disease-Specific Survival and Patterns of Relapse in Endometrial Cancer.","authors":"Annukka Pasanen, Taru Tuomi, Jorma Isola, Synnöve Staff, Ralf Bützow, Mikko Loukovaara","doi":"10.1097/IGC.0000000000000801","DOIUrl":"10.1097/IGC.0000000000000801","url":null,"abstract":"<p><strong>Objective: </strong>The aim was to study the association of L1 cell adhesion molecule (L1CAM) expression with the outcome of patients with endometrial cancer, especially with regard to conventional risk variables, and to compare the patterns of relapse in L1CAM-positive and -negative cancers.</p><p><strong>Methods: </strong>This was a retrospective study of 805 women. The Kaplan-Meier method and univariate and multivariate Cox regression models were applied for survival analyses. Missing data were replaced using multiple imputation. The median follow-up time was 51 months (range, 1-98).</p><p><strong>Results: </strong>One hundred twenty-one (15.0%) cases were L1CAM positive. L1CAM positivity was associated with high stage (I vs II-IV) (odds ratio [OR], 2.3), lymph node involvement (OR, 2.9), poor differentiation (OR, 6.1), non-endometrioid histology (OR, 9.9), lymphovascular space invasion (OR, 2.8), cervical stromal invasion (OR, 1.8), positive peritoneal cytology (OR, 4.1), and age older than 65 years (OR, 2.8). The frequencies of deep myometrial invasion (50% or deeper), tumor size 2 cm or greater, and body mass index 30 kg/m or greater were not significantly different between L1CAM-positive and -negative cases. L1CAM predicted poor disease-specific survival in endometrioid (P < 0.0001) but not in non-endometrioid carcinomas (P = 0.934). The negative impact of L1CAM on outcome was confirmed in a Cox multivariate disease-specific survival analysis. Univariate survival analyses in the different ESMO-ESGO-ESTRO endometrial cancer risk groups showed an association between L1CAM positivity and poor outcome in intermediate (hazard ratio, 12) and high-risk advanced metastatic (hazard ratio, 2.0) groups. Extra-abdominal relapses were more frequent in L1CAM-positive (13.2%) than L1CAM-negative (1.9%) stage I endometrioid carcinomas (P < 0.0001), whereas other site-specific relapses in local cancers were L1CAM independent.</p><p><strong>Conclusions: </strong>L1CAM is associated with the occurrence of poor prognostic variables and predicts advanced disease in endometrial cancer. L1CAM predicts extra-abdominal relapses and poor survival in endometrioid endometrial cancer, but seems not to be a prognostic factor in non-endometrioid carcinomas.</p>","PeriodicalId":13983,"journal":{"name":"International Journal of Gynecologic Cancer","volume":"54 1","pages":"1465-71"},"PeriodicalIF":0.0,"publicationDate":"2016-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78905090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaginal Radical Trachelectomy for Early-Stage Cervical Cancer: Increased Recurrence Risk for Adenocarcinoma.","authors":"Petra L M Zusterzeel, Fraukje J M Pol, Maaike van Ham, Ronald P Zweemer, Ruud L M Bekkers, Leon F A G Massuger, René H M Verheijen","doi":"10.1097/IGC.0000000000000763","DOIUrl":"10.1097/IGC.0000000000000763","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate consecutive vaginal radical trachelectomies (VRTs) in early-stage cervical cancer in the 2 main referral centers for fertility-preserving surgery in the Netherlands.</p><p><strong>Materials and methods: </strong>Oncology, fertility, and obstetrical data were recorded in a regional database of all VRTs without neoadjuvant chemotherapy performed in 2 major referral centers between 2000 and 2015.</p><p><strong>Results: </strong>Most of the patients (91.7%) had stage IB1 disease. In 72.0%, squamous cell carcinoma was the histologic diagnosis; in 24.2%, adenocarcinoma; and in 3.8%, adenosquamous carcinoma. The median follow-up was 51 months.Nine (6.8%) recurrences occurred, 4 resulting in death of disease (death rate, 3.0%). Recurrence rates were 12.5% for adenocarcinoma, 20% for adenosquamous carcinoma, and 4.2% for squamous cell carcinoma (P < 0.01).From 117 women, data about fertility and obstetrical outcome were obtained. Almost 60% of women attempted to conceive after a VRT. Of these women, 40% needed fertility treatment. A total of 47 pregnancies were established, and a total of 37 children were born of which 30 (81.1%) were delivered after 32 weeks of gestational age.</p><p><strong>Conclusions: </strong>Nonsquamous cell histology and high-grade disease are associated with a significantly higher risk of recurrence in the univariate and multivariate analyses. Women with both these histology features should be counseled reticently for VRT.Pregnancies after VRT must be regarded as high-risk pregnancies with a high prematurity rate.</p>","PeriodicalId":13983,"journal":{"name":"International Journal of Gynecologic Cancer","volume":"4 1","pages":"1293-9"},"PeriodicalIF":0.0,"publicationDate":"2016-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89183124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypomagnesemia Is Prevalent in Patients Undergoing Gynecologic Surgery by a Gynecologic Oncologist.","authors":"Michael A Ulm, Catherine H Watson, Prethi Vaddadi, Jim Y Wan, Joseph T Santoso","doi":"10.1097/IGC.0000000000000766","DOIUrl":"10.1097/IGC.0000000000000766","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to assess the incidence of and risk factors for hypomagnesemia in patients undergoing gynecologic surgery by a gynecologic oncologist.</p><p><strong>Methods: </strong>A retrospective chart review was performed on all patients undergoing surgery for gynecologic pathology from July 2011 to July 2015 by a single surgeon. Demographic data, surgical indication, surgery performed, preoperative laboratory values, postoperative laboratory values, and medical history were examined. Hypomagnesemia was defined as less than 1.8 mg/dL. Hypermagnesemia was defined as greater than 2.5 mg/dL.</p><p><strong>Results: </strong>Six hundred sixty-nine patients were identified for analysis. One hundred ninety-seven patients had hypomagnesemia (29.4%). Four hundred sixty-six patients had normal magnesium levels (69.5%), and 6 patients had hypermagnesemia (1%). Among patients with benign disease, 24.9% had preoperative hypomagnesemia compared with 32.7% of patients with a gynecologic malignancy. African American race (P = 0.041), diabetes mellitus (P < 0.001), and malignancy (P = 0.029) were all associated with preoperative hypomagnesemia. Diabetes and major surgery were associated with postoperative hypomagnesemia (P = 0.012 and P = 0.048, respectively). Hypomagnesemia was associated with increased preoperative and postoperative pain (P = 0.049 and P < 0.001, respectively) as well as postoperative hypokalemia (P = 0.001). Age, body mass index, hypertension, cancer type, hematocrit, surgical indication, and length of hospital stay were not associated with hypomagnesemia.</p><p><strong>Conclusions: </strong>Perioperative hypomagnesemia is prevalent in patients undergoing gynecologic surgery by a gynecologic oncology, especially in patients who have a gynecologic malignancy. We recommend routine preoperative and postoperative evaluation of serum magnesium in all patients undergoing gynecologic surgery by a gynecologic oncologist.</p>","PeriodicalId":13983,"journal":{"name":"International Journal of Gynecologic Cancer","volume":"399 1","pages":"1320-6"},"PeriodicalIF":0.0,"publicationDate":"2016-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84842562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Combination of Preoperative Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography and Sentinel Lymph Node Mapping in the Surgical Management of Endometrioid Endometrial Cancer.","authors":"Tugan Bese, Veysel Sal, Fuat Demirkiran, Ilker Kahramanoglu, Nedim Tokgozoglu, Sennur Ilvan, Ovgu Aydin, Metin Hallac, Betul Vatankulu, Gokhan Demirayak, Hasan Turan, Macit Arvas","doi":"10.1097/IGC.0000000000000773","DOIUrl":"10.1097/IGC.0000000000000773","url":null,"abstract":"<p><strong>Objective: </strong>The goal of this study was to evaluate the combination of sentinel lymph node (SLN) mapping and F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan in detection of lymph node involvement in patients with endometrioid endometrial cancer (EEC).</p><p><strong>Methods/materials: </strong>Ninety-five patients with EEC who had preoperative PET/CT imaging and underwent SLN mapping were retrospectively analyzed. Methylene blue dye was used and injected to the cervix at 3- and 9-o'clock positions (a total of 4 mL). Pelvic lymphadenectomy was performed on all of the patients after SLN mapping. If the SLN was negative in the initial hematoxylin and eosin staining, an ultrastaging study was performed for the SLNs.</p><p><strong>Results: </strong>Sentinel lymph nodes were detected in 77 (81.1%) of 95 patients, with a mean of 2.95 SLNs. There was only 1 case (1.4%) with a positive SLN in the intraoperative frozen section examination in those patients with negative PET/CT findings and in whom SLNs were detected (n = 70). Among the remaining 69 patients with negative preoperative PET/CT findings and negative frozen section results for the SLNs, there were 2 patients with SLN involvement in the final ultrastaging pathology. In the patient-based analyses, the sensitivity, specificity, and positive and negative predictive values of the PET/CT and SLN frozen section were 33%, 100%, 100%, and 97.1%, respectively.</p><p><strong>Conclusions: </strong>As no metastases in the nonsentinel pelvic lymph nodes were found in patients with EEC who had both negative PET/CT findings and frozen section results of the SLNs in both hemipelvises, we suggest using both methods to reduce the incidence of unnecessary systematic lymphadenectomy.</p>","PeriodicalId":13983,"journal":{"name":"International Journal of Gynecologic Cancer","volume":"45 1","pages":"1228-38"},"PeriodicalIF":0.0,"publicationDate":"2016-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84704194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase I Clinical Study of Irinotecan Plus S-1 in Patients With Advanced or Recurrent Cervical Cancer Previously Treated With Platinum-Based Chemotherapy.","authors":"Seiji Mabuchi, Eriko Yokoi, Takao Owa, Katsumi Kozasa, Michiko Yamashita, Eiji Kobayashi, Takuji Tomimatsu, Takeshi Yoki, Tateki Tsutui, Tadashi Kimura","doi":"10.1097/IGC.0000000000000769","DOIUrl":"10.1097/IGC.0000000000000769","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to determine the maximum tolerated dose and acute dose-limiting toxicities (DLTs) of intravenous irinotecan plus oral S-1 in patients with advanced or recurrent uterine cervical cancer.</p><p><strong>Methods: </strong>Irinotecan was administered intravenously over the course of 90 minutes on day 1, and S-1 was given orally in 2 divided doses from days 1 to 14 of a 21-day cycle. The dose of S-1 was escalated in a stepwise fashion from 40 (level 1) to 60 mg/m (level 2) and then 80 mg/m (level 3), whereas the dosage of irinotecan remained the same (150 mg/m). The primary end point for the escalation study was acute DLT that occurred within 2 cycles of chemotherapy.</p><p><strong>Results: </strong>Twelve patients were enrolled and treated over 3 dose levels. Their median age was 47 years (range, 28-48 years). At level 1, one episode of grade 3 anemia and a grade 3 fatigue were observed, but no DLT developed. At level 2, the first patient experienced febrile neutropenia, which was considered to be a DLT. To evaluate the toxicity of this dose level, 5 more patients were evaluated. However, no DLT developed in these patients. At level 3, although grade 1 to 2 hematological and nonhematological toxicities developed, no DLT occurred.</p><p><strong>Conclusions: </strong>In women with advanced or recurrent cervical cancer previously treated with platinum-based chemotherapy, S-1 plus irinotecan in a triweekly setting is a reasonable treatment regimen with an acceptable toxicity profile. The recommended doses of S-1 and irinotecan for this regimen are 80 and 150 mg/m, respectively.</p>","PeriodicalId":13983,"journal":{"name":"International Journal of Gynecologic Cancer","volume":"60 1","pages":"1281-7"},"PeriodicalIF":0.0,"publicationDate":"2016-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82431631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin Increases E-cadherin in Tumors of Diabetic Patients With Endometrial Cancer and Suppresses Epithelial-Mesenchymal Transition in Endometrial Cancer Cell Lines.","authors":"Ido Laskov, Paul Abou-Nader, Oreekha Amin, Charles-Andre Philip, Marie-Claude Beauchamp, Amber Yasmeen, Walter H Gotlieb","doi":"10.1097/IGC.0000000000000761","DOIUrl":"10.1097/IGC.0000000000000761","url":null,"abstract":"<p><strong>Purpose: </strong>Epithelial-mesenchymal transition (EMT) is a critical process for cancer metastasis and recurrence. Metformin, an effective oral antidiabetic drug, has been associated with decreased cancer risk and mortality. In this pilot study, we started to evaluate the effect of metformin on EMT in vivo and in vitro in endometrial cancer (EC).</p><p><strong>Methods: </strong>Endometrial cancer cell lines and freshly isolated EC tumor specimens were used to assess EMT after metformin treatment. Cell lines were subjected to wound healing and AlamarBlue assays to determine cell migration and cell proliferation; messenger RNA levels were measured by real-time reverse transcriptase (RT) quantitative polymerase chain reaction (PCR), and protein levels were measured by Western blots to detect EMT marker expression.</p><p><strong>Results: </strong>Protein expression and messenger RNA of E-cadherin was found to be increased (P = 0.02 and 0.04, respectively) in 30 EC tumor specimens of diabetic patients treated with metformin compared with 20 EC tumor specimens of diabetic patients treated with other antidiabetic agents. In vitro, metformin reduced cell migration at 5 mM for 48 hours, as determined by the wound healing assay in EC cell lines (Ishikawa, 45% reduction; HEC50, 40% reduction), whereas more than 90% of the cells remained viable on the AlamarBlue assay. Metformin reduced EMT in the cell lines and regulated the expression of the EMT-related epithelial markers, E-cadherin and Pan-keratin; the mesenchymal markers, N-cadherin, fibronectin, and vimentin; and the EMT drivers, Twist-1, snail-1, and ZEB-1.</p><p><strong>Conclusions: </strong>Tumors of patients on metformin have increased E-cadherin expression, and metformin decreases EMT in EC cell lines in vitro, suggesting clinical biological relevance of metformin in women with EC.</p>","PeriodicalId":13983,"journal":{"name":"International Journal of Gynecologic Cancer","volume":"214 1","pages":"1213-21"},"PeriodicalIF":0.0,"publicationDate":"2016-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73422629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}