scholarly journals Prevalence and prognostic role of mismatch repair gene defect in endometrial cancer patients

Tumor Biology ◽  
2017 ◽  
Vol 39 (9) ◽  
pp. 101042831772583 ◽  
Author(s):  
Siriwan Tangjitgamol ◽  
Thannaporn Kittisiam ◽  
Sujitra Tanvanich
Keyword(s):  
Endometrial Cancer ◽  
Confidence Interval ◽  
Mismatch Repair ◽  
Early Stage ◽  
Progression Free Survival ◽  
Mismatch Repair Gene ◽  
Gene Defect ◽  
Cancer Specific Survival ◽  
Repair Gene ◽  
Free Survival

The study was to evaluate the prevalence of mismatch repair gene defect among Thai patients with endometrial cancer and its association with clinico-pathological features and survivals. The formalin fixed paraffin-embedded blocks of EMC tissue from hysterectomy specimens of patients having surgery in our institution between 1 Jan 1995 and 31 December 2016 were assessed for the immunohistochemical expression of 4 mismatch repair proteins (MLH1, PMS, MSH2, MSH 6). Mismatch repair gene defect was determined by a negative expression of at least 1 protein. Among 385 EMC patients included in the study, mean age was 57.3 ± 10.8 years with 62.3% aged ⩽ 60 years. The most frequent mismatch repair gene defect was MSH6 (38.7%), followed by PMS2 (34.3%), MLH1 (33.2%), and MSH2 (16.4%). Overall, 55.1% showed negative expression of at least one protein. We found significantly higher mismatch repair gene defect in patients aged ⩽ 60 years, with early stage disease, and negative lymph node status than the other comparative groups: 59.2% vs 48.3% for age (p = 0.037), 58.2% vs 45.2% (p = 0.027) for stage, and 58.1% vs 44.6% (p = 0.048) for nodal status. The 5-year progression-free survival, overall survival, and endometrial cancer-specific survival of patients with mismatch repair gene defect was higher than those without gene defect. The differences were statistically significant for only progression-free survival and endometrial cancer-specific survival: 87.7% (95% confidence interval = 83.0%–92.4%) vs 81.5% (95% confidence interval = 75.4%–87.6%) (p = 0.049) for progression-free survival and 91.0% (95% confidence interval = 86.9%–95.1%) vs 85.5% (95% confidence interval = 80.0%–91.0%) (p = 0.044) for endometrial cancer-specific survival, respectively. In conclusion, more than half of Thai endometrial cancer patients had mismatch repair gene defect. The patients with mismatch repair gene defect had significantly younger age (⩽ 60 years) and better prognosis in terms of early stage, negative nodal status, and longer survivals.

Why Routine Clinical Follow-up for Patients With Early Stage Endometrial Cancer Is Not Always Necessary: A Study on Women in South Wales

2014 ◽  
Vol 24 (3) ◽  
pp. 556-563 ◽  
Author(s):  
Lilly Aung ◽  
Robert E.J. Howells ◽  
Kenneth C.K. Lim ◽  
Emma Hudson ◽  
Peter W. Jones
Keyword(s):  
Endometrial Cancer ◽  
Confidence Interval ◽  
Endometrial Carcinoma ◽  
Early Stage ◽  
Progression Free Survival ◽  
Disease Recurrence ◽  
Hazard Ratio ◽  
Free Survival ◽  
South Wales

ObjectiveThis study aimed to examine the existing methods of follow-up in women who have undergone treatment of early endometrial carcinoma in South Wales and to assess if they are appropriate.DesignThis study used a retrospective analysis of follow-up data.SettingThis study was performed in the Virtual Gynaecological Oncology Centre, South Wales, United Kingdom.SampleThis study sample is composed of 552 women.MethodsData regarding follow-up were collected retrospectively from patient case notes and computerized data systems. Data were analyzed using the Pearson χ2 test, Cox proportional hazard regression analysis, and Kaplan-Meier curves.Main Outcome MeasuresThis study aimed to determine whether routine follow-up was beneficial in detecting disease recurrence and whether outcome was influenced by routine follow-up.ResultsBetween January 1, 2000, and December 31, 2010, 552 women were treated for early stage endometrial carcinoma. The 5-year survival was 81%, and the 5-year progression-free survival was 77%. Of these 552 women, 81 (15%) developed a disease recurrence; the majority (61/81 [75%]) recurred within 3 years. The median survival was 35 months compared with 47 months in patients who did not develop a recurrence. Of the 81 patients, 73 (90%) were symptomatic and only 5 patients were truly asymptomatic at follow-up. The most important and significant prognostic factor was “recurrent disease” with overall survival (hazard ratio, 2.20; P < 0.001; 95% confidence interval, 1.75–2.65) and progression-free survival (hazard ratio, 2.52; P < 0.001; 95% confidence interval, 2.09–2.95). “Asymptomatic recurrence” was not an independent predictor of outcome.ConclusionsRoutine follow-up for early endometrial cancer is not beneficial for patients because most were symptomatic at the time of detection. It does not significantly improve the outcome. We propose altering the follow-up time regimen and adopting alternative follow-up strategies for women in South Wales.

scholarly journals Body Mass Index in Early Adulthood and Endometrial Cancer Risk for Mismatch Repair Gene Mutation Carriers

2011 ◽  
Vol 117 (4) ◽  
pp. 899-905 ◽  
Author(s):  
Aung Ko Win ◽  
James G. Dowty ◽  
Yoland C. Antill ◽  
Dallas R. English ◽  
John A. Baron ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Endometrial Cancer ◽  
Cancer Risk ◽  
Mismatch Repair ◽  
Gene Mutation ◽  
Body Mass ◽  
Early Adulthood ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
Endometrial Cancer Risk

A Phase 2, Randomized, Open-Label Study of Irosustat Versus Megestrol Acetate in Advanced Endometrial Cancer

2017 ◽  
Vol 27 (2) ◽  
pp. 258-266 ◽  
Author(s):  
Patricia Pautier ◽  
Ignace Vergote ◽  
Florence Joly ◽  
Bohuslav Melichar ◽  
Elzbieta Kutarska ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Adverse Events ◽  
Confidence Interval ◽  
Progression Free Survival ◽  
Megestrol Acetate ◽  
Phase 2 ◽  
Open Label ◽  
Free Survival ◽  
Recurrent Endometrial Cancer

ObjectiveAdvanced/metastatic or recurrent endometrial cancer has a poor prognosis. Malignant endometrial tissue has high steroid sulphatase (STS) activity. The aim of this study was to evaluate STS as a therapeutic target in patients with endometrial cancer.MethodsThis was a phase 2, multicenter, international, open-label, randomized (1:1), 2-arm study of the STS inhibitor oral irosustat 40 mg/d versus oral megestrol acetate 160 mg/d in women with advanced/metastatic or recurrent estrogen receptor–positive endometrial cancer. The primary end point was the proportion of patients without progression or death 6 months after start of treatment. Secondary end points included progression-free survival, time to progression, overall survival, and safety.ResultsSeventy-one patients were treated (36 with irosustat, 35 with megestrol acetate). The study was prematurely stopped after futility analysis. Overall, 36.1% and 54.1% of patients receiving irosustat or megestrol acetate had not progressed or died at 6 months, respectively. There were no statistically significant differences between irosustat and megestrol acetate in response and overall survival rates. Irosustat patients had a median progression-free survival of 16 weeks (90% confidence interval, 9.0–31.4) versus 40 weeks (90% confidence interval, 16.3–64.0) in megestrol acetate patients. Treatment-related adverse events occurred in 20 (55.6%) and 13 (37.1%) patients receiving irosustat or megestrol, respectively. Most adverse events in both groups were grade 1 or 2.ConclusionsAlthough irosustat monotherapy did not attain a level of activity sufficient for further development in patients with advanced/recurrent endometrial cancer, this study confirms the activity of hormonal treatment (megestrol acetate) for this indication.

Constitutional Mismatch Repair Gene Defect Syndrome Presenting With Adenomatous Polyposis and Cafe au Lait Spots: A Case Report

2019 ◽  
Vol 42 (7) ◽  
pp. e689-e691
Author(s):  
Elif Sağ ◽  
Murat Erkut ◽  
İsmail Saygin ◽  
Alper Han Çebi ◽  
Aysenur Bahadir ◽  
...  
Keyword(s):  
Case Report ◽  
Mismatch Repair ◽  
Mismatch Repair Gene ◽  
Adenomatous Polyposis ◽  
Gene Defect ◽  
Repair Gene ◽  
Café Au Lait Spots

A polymorphism within the mismatch repair gene predicts prognosis and adjuvant chemotherapy benefit in gastric cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3025-3025
Author(s):  
Deqiang Wang ◽  
Deyu Chen ◽  
Bo Shen ◽  
Xiaofeng Chen ◽  
Mingzhe Xiao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Mismatch Repair ◽  
Patient Selection ◽  
Early Stage ◽  
Predictive Biomarkers ◽  
Mismatch Repair Gene ◽  
Poor Overall Survival ◽  
Repair Gene ◽  
The Impact

3025 Background: Radical surgery with subsequent adjuvant chemotherapy was effective treatment for early-stage gastric cancer (GC) patients. Unfortunately, after optimal multimodality therapy, up to 30% to 40% of patients undergoing resection will relapse within 5 years. There are no validated prognostic and predictive biomarkers for GC patients who receive adjuvant chemotherapy, and current patient selection is based mainly on postoperative pathological staging. Defective mismatch repair (MMR) or microsatellite instability (MSI) may affect GC outcome. Polymorphisms of MMR genes with a low-penetrant effect can cause heterogeneous MMR capability among individuals. It is not known about the impact of these polymorphisms on GC outcome. Methods: The polymorphisms rs1800734 in MLH1, rs2303428 and rs3732183 in MSH2, rs735943 in EXO1, and rs11797 in TREX1 were selected and analyzed in independent discovery and validation sets that included 167 and 593 patients, respectively. MSI was determined. Results: In the discovery set, both the rs2303428 TC+CC and the rs11797 GA+AA genotypes significantly correlated with poor overall survival (OS; P < 0.05). In the validation set, we confirmed the prognostic association for the rs2303428 TC+CC genotype (P = 0.036) but not for the rs11797 GA+AA genotype (P = 0.737). Furthermore, the prognostic role of the rs2303428 TC+CC genotype was observed in non-cardia (P = 0.005) but not in cardia GC (P = 0.934). The multivariate model showed that the rs2303428 TC+CC genotype was an independent predictor for OS in non-cardia patients (HR = 1.54; 95% CI: 1.02-2.32; P = 0.040). Moreover, fluoropyrimidines-based adjuvant chemotherapy significantly improved OS (HR = 0.29; 95% CI: 0.15-0.58; P < 0.001) for non-cardia patients with the rs2303428 TC+CC genotype but not for those with the rs2303428 TT genotype. The rs2303428 genotypes were not associated with MSI frequency. Conclusions: The rs2303428 TC+CC genotype may predict prognosis and adjuvant chemotherapy benefit in non-cardia GC patients independent of MSI. To our knowledge, our study is the first to report the prognostic and predictive roles of MMR genotype in GC. Although prospective validation is necessary, our findings have the potential to improve patient selection for adjuvant chemotherapy and spare large numbers of GC patients’ unnecessary therapy.

Definitive radiotherapy for vaginal recurrence of early-stage endometrial cancer: survival outcomes and effect of mismatch repair status

2021 ◽  
pp. ijgc-2021-002536
Author(s):  
Gabriela Alban ◽  
Teresa Cheng ◽  
Jenna Adleman ◽  
Ivan Buzurovic ◽  
Jennifer Pretz ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Mismatch Repair ◽  
Early Stage ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Definitive Radiotherapy ◽  
Image Guided ◽  
Early Stage Endometrial Cancer ◽  
Vaginal Recurrence

ObjectiveTo evaluate clinical outcomes, prognostic factors, and toxicity in patients with vaginal recurrence of early-stage endometrial cancer treated with definitive radiotherapy.MethodsRetrospective review identified 62 patients with stage I–II endometrial cancer and vaginal recurrence treated with external beam radiotherapy and image-guided brachytherapy with definitive intent from November 2004 to July 2017. All patients had prior hysterectomy without adjuvant radiotherapy and >3 months follow-up. Mismatch repair (MMR) status was determined by immunohistochemical staining of the four mismatch repair proteins (MLH1, MSH2, PMS2, and MSH6) when available in the pathology record. Rates of vaginal control, recurrence-free survival, and overall survival were calculated by Kaplan–Meier. Univariate and multivariate analyses were performed by Cox proportional hazards.ResultsMost patients had endometrioid histology (55, 89%), grade 1 or 2 tumor (53, 85%), and vaginal-only recurrence (55, 89%). With a median follow-up of 39 months (range, 3–167), 3- and 5-year rates of vaginal control, recurrence-free survival, and overall survival were 86% and 82%, 69% and 55%, and 80% and 61%, respectively. On multivariate analysis, non-endometrioid histology (HR 12.5, P<0.01) was associated with relapse when adjusted for chemotherapy use. Patients with non-endometrioid histology also had a 4.5-fold higher risk of death when adjusted for age (P=0.02). Twenty patients had known MMR status, all with grade 1–2 endometrioid tumors and 10 (50%) with MMR deficiency. The 3-year recurrence-free survival was 100% for MMR-proficient tumors and 52% for MMR-deficient (P=0.03). Late grade 2 and 3 gastrointestinal, genitourinary and vaginal toxicity was reported in 27% and 3%, 15% and 2%, and 16% and 2% of patients, respectively.ConclusionDefinitive radiotherapy with image-guided brachytherapy resulted in 5-year local control rates exceeding 80% and late severe toxicity rates were under 3%. Distant recurrence was common and highest for those with grade 3 or non-endometrioid tumors and MMR deficient grade 1–2 disease.

scholarly journals Pathologic and Treatment Outcomes Among a Geriatric Population of Endometrial Cancer Patients: An NRG Oncology/Gynecologic Oncology Group Ancillary Data Analysis of LAP2

2017 ◽  
Vol 27 (4) ◽  
pp. 730-737 ◽  
Author(s):  
Erin A. Bishop ◽  
James J. Java ◽  
Kathleen N. Moore ◽  
Joan L. Walker
Keyword(s):  
Endometrial Cancer ◽  
Adjuvant Therapy ◽  
Cancer Patients ◽  
Early Stage ◽  
Gynecologic Oncology ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Gynecologic Oncology Group ◽  
Free Survival ◽  
Early Stage Endometrial Cancer

ObjectivesElderly endometrial cancer patients have worse disease-specific survival than their younger counterparts, but the cause for this discrepancy is unknown. The goal of this analysis is to compare outcomes by age in a fully staged elderly endometrial cancer population.Methods/MaterialsThis is an analysis of patients on Gynecologic Oncology Group Study (GOG) LAP2, which included clinically early stage endometrial cancer patients randomized to laparotomy versus laparoscopy for surgical staging. Patients were divided into risk groups based on criteria defined by GOG protocol 99. Differences in outcomes and adjuvant therapy were assessed within these risk groups.ResultsLAP2 included 715 patients 70 years or older. With increasing age, worse tumor characteristics were seen. Older patients received similar rates of adjuvant therapy when stratified by stage. Patients 70 years or older had significantly worse progression-free survival and overall survival, and on multivariate analysis, older age and high-risk uterine factors were predictors of progression-free survival and overall survival, whereas stage and lymph node metastases were not. When patients were divided into GOG protocol 99 risk categories, most of those who met the high-intermediate risk criteria did so based on age above 70 years and grade 2 to 3 disease. These patients had low risk of recurrence (3.3%) compared with those who met the criteria by age above 70 years and all 3 uterine factors (20.9%).ConclusionsIn early stage endometrial cancer, patients 70 years or older who undergo similar surgical management and adjuvant therapy, age and tumor characteristics independently predict recurrence. Most patients older than 70 years meet the high-intermediate risk criteria for recurrence based on age and 1 other uterine risk factor, and our results suggest that these patients are at low risk for recurrence.

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