Lynch Syndrome Identification in Endometrial Cancer Patients: Should Universal Screening be Used for all Histologies?

2021 ◽  
Vol 17 ◽  
Author(s):  
Jessica E. Parker ◽  
Caitlin Mauer ◽  
Wenxin Zheng ◽  
David S. Miller ◽  
Jayanthi S. Lea
Keyword(s):  
Endometrial Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Lynch Syndrome ◽  
Cancer Patients ◽  
Universal Screening ◽  
Type I ◽  
Type Ii ◽  
Screening Approach ◽  
Endometrial Cancers

Background: There is an increased proportion of non-endometrioid histologies in Lynch syndrome-associated compared to sporadic endometrial cancer, however screening recommendations do not differ between type I and type II cancers. Objective: Our objective was to examine the frequency of Lynch syndrome identified in type I and type II endometrial cancers and their associated characteristics. Methods: We reviewed patients with type I and type II endometrial cancer who were screened for Lynch Syndrome or referred for genetic testing according to an age and family-history based screening protocol. All patients were seen and treated at large academic institution affiliated with a county safety-net hospital. Clinical, pathologic, immunohistochemistry, and germline genetic testing results were obtained as well as choice of genetic screening approach, personal and family history, and compliance with testing. Results: 234 women with type I and 29 patients with type II endometrial cancer were identified. Lynch syndrome was diagnosed in a total of eight (3.4%) type I endometrial cancer patients, all identified after age-based tumor screening. In the type II endometrial cancer group, three (10.3%) patients had Lynch syndrome. One was referred for testing after abnormal immunohistochemistry screening under age 60. The other two were >60 years old and identified after abnormal immunohistochemistry screening performed by physician request. Conclusion: Age based screening may not diagnose Lynch Syndrome in women with type II endometrial cancers. Our findings underscore the need for a universal screening approach in patients with type II endometrial cancers, even in a low resource population.

scholarly journals Combined genetic mutations and DNA-methylated genes as biomarkers for endometrial cancer detection from cervical scrapings

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Phui-Ly Liew ◽  
Rui-Lan Huang ◽  
Tzu-I Wu ◽  
Chi-Chun Liao ◽  
Chien-Wen Chen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Endometrial Cancer ◽  
Cancer Detection ◽  
Type I ◽  
Type Ii ◽  
Normal Endometrium ◽  
Epigenetic Biomarkers ◽  
Pap Smear Screening ◽  
Endometrial Cancers ◽  
Endometrial Carcinomas

Abstract Background Endometrial cancer is a common gynecologic cancer. Noninvasive molecular biomarkers for triage of high-risk patients for invasive procedures are needed. Based on the success of cytological Pap smear screening, cervical scrapings are a good source of DNA for molecular testing. In addition to genetic lesions, DNA methylation is a promising biomarker. We assessed the usefulness of combining genetic and epigenetic biomarkers from cervical scrapings to detect endometrial carcinomas. Methods We performed a retrospective case–control study of 96 consecutive cervical scrapings from patients with abnormal uterine bleeding who underwent surgery for diagnostic evaluation. Thirty and 16 cases were diagnosed with type I and type II endometrial cancers, respectively. The remaining non-cancer cases included normal endometrium (n = 12), benign uterine lesions (n = 20), and endometrial hyperplasia (n = 18). Quantitative methylation-specific PCR and mass spectrometry were used for DNA methylation and genetic mutation analysis. Logistic regression was used to evaluate the clinical performance of these candidate biomarkers. Results We tested the effectiveness of the methylation status of four genes (BHLHE22, CDO1, TBX5, and HAND2) in endometrial cancer detection. The area under the receiver operating characteristic curves ranged from 0.703 to 0.878, and panels of hypermethylated BHLHE22/CDO1/HAND2 (87.0% sensitivity and 86.0% specificity) and BHLHE22/CDO1/TBX5 (89.1% sensitivity and 80.0% specificity) showed significant differences and could distinguish benign from malignant endometrial lesions. The sensitivity and specificity in endometrial cancer detection for BHLHE22/CDO1 were 84.8% and 88.0%, respectively. Both type I and II endometrial carcinomas could be detected using a BHLHE22/CDO1-based methylation profile, suggesting that they may have common epigenomes. Moreover, PTEN and TP53 mutations were found in 63.3% of type I and 93.6% of type II endometrial cancers. Unexpectedly, PTEN and TP53 mutations were commonly found in cervical scrapings of the normal endometrium (25% and 33.3%, respectively) and in cases with benign uterine lesions (10% and 50%, respectively). Finally, combinations of any one mutation of PTEN and TP53 mutations had a sensitivity of 91.3%, but a specificity of only 42.0%. Conclusions Adding PTEN/TP53 mutation testing to BHLHE22/CDO1-based methylation testing did not improve the detection of endometrial cancer.

P.02.21 EARLY- ONSET ENDOMETRIAL CANCER PATIENTS ARE AT HIGH RISK FOR LYNCH SYNDROME REGARDLESS OF FAMILY HISTORY

2019 ◽  
Vol 51 ◽  
pp. e156-e157
Author(s):  
L. Sanchez Mete ◽  
G. Vocaturo ◽  
A. Martayan ◽  
B. Casini ◽  
M. Diodoro ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Family History ◽  
High Risk ◽  
Lynch Syndrome ◽  
Cancer Patients ◽  
Early Onset

scholarly journals Correlation of Leptin, Proinflammatory Cytokines and Oxidative Stress with Tumor Size and Disease Stage of Endometrioid (Type I) Endometrial Cancer and Review of the Underlying Mechanisms

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 268
Author(s):  
Clelia Madeddu ◽  
Elisabetta Sanna ◽  
Giulia Gramignano ◽  
Luciana Tanca ◽  
Maria Cristina Cherchi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endometrial Cancer ◽  
Prognostic Factors ◽  
Cancer Patients ◽  
Proinflammatory Cytokines ◽  
Disease Stage ◽  
Type I ◽  
Type Ii ◽  
Endometrioid Endometrial Cancer ◽  
And Oxidative Stress

Endometrioid endometrial cancer is associated with increased BMI and obesity through multiple pathogenetic mechanisms involving hyperestrogenism, hyperinsulinemia, altered adipokine secretion, inflammation, and oxidative stress. In the present study, we aimed to investigate the correlation between BMI, leptin, the proinflammatory cytokines IL-6 and TNFα, reactive oxygen species (ROS), and the traditional prognostic factors T, G, N and M status among type I endometrioid and type II endometrial cancer patients. We enrolled 305 consecutive endometrial cancer patients prospectively. We found that BMI, leptin, and IL-6 significantly correlated with T status, N status, and M status among endometrioid type I endometrial cancer patients. Among type II endometrial cancer patients, BMI and leptin did not correlate with any of the prognostic parameters, whereas there was a positive correlation between IL-6 and the presence of distant metastases. In the multivariate regression analysis, BMI, leptin, and IL-6 were independent predictive variables of T, N, and M status in endometrioid type I endometrial cancer patients. Our study demonstrates that weight gain, adiposity-related adipokines, inflammation, and oxidative stress correlate with the prognostic factors of endometrioid endometrial cancer. Knowledge of the role of obesity-related biological pathways and mediators in the pathogenesis and prognosis of endometrioid endometrial malignancies may offer new perspectives on combined therapeutic strategies that have not been explored to date, both in the advanced disease and in the adjuvant setting.

scholarly journals Type I and II Endometrial Cancers: Have They Different Risk Factors?

2013 ◽  
Vol 31 (20) ◽  
pp. 2607-2618 ◽  
Author(s):  
Veronica Wendy Setiawan ◽  
Hannah P. Yang ◽  
Malcolm C. Pike ◽  
Susan E. McCann ◽  
Herbert Yu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Endometrial Cancer ◽  
Pooled Analysis ◽  
Age At Menarche ◽  
Type I ◽  
Type Ii ◽  
Case Control Studies ◽  
Mixed Cell ◽  
Cancer Risk Factors ◽  
Endometrial Cancers

Purpose Endometrial cancers have long been divided into estrogen-dependent type I and the less common clinically aggressive estrogen-independent type II. Little is known about risk factors for type II tumors because most studies lack sufficient cases to study these much less common tumors separately. We examined whether so-called classical endometrial cancer risk factors also influence the risk of type II tumors. Patients and Methods Individual-level data from 10 cohort and 14 case-control studies from the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 14,069 endometrial cancer cases and 35,312 controls were included. We classified endometrioid (n = 7,246), adenocarcinoma not otherwise specified (n = 4,830), and adenocarcinoma with squamous differentiation (n = 777) as type I tumors and serous (n = 508) and mixed cell (n = 346) as type II tumors. Results Parity, oral contraceptive use, cigarette smoking, age at menarche, and diabetes were associated with type I and type II tumors to similar extents. Body mass index, however, had a greater effect on type I tumors than on type II tumors: odds ratio (OR) per 2 kg/m2 increase was 1.20 (95% CI, 1.19 to 1.21) for type I and 1.12 (95% CI, 1.09 to 1.14) for type II tumors (Pheterogeneity < .0001). Risk factor patterns for high-grade endometrioid tumors and type II tumors were similar. Conclusion The results of this pooled analysis suggest that the two endometrial cancer types share many common etiologic factors. The etiology of type II tumors may, therefore, not be completely estrogen independent, as previously believed.

CD8, FoxP3, and CD45RO+ Lymphocytic Infiltrates in Type I and Type II Endometrial Cancers in African American and European American Females

2017 ◽  
Vol 36 (6) ◽  
pp. 540-549 ◽  
Author(s):  
Tariq Rashid ◽  
Jennifer L. Young-Pierce ◽  
Elizabeth Garrett-Mayer ◽  
Whitney Graybill ◽  
Shelby Neal ◽  
...  
Keyword(s):  
African American ◽  
European American ◽  
Type I ◽  
Type Ii ◽  
Endometrial Cancers ◽  
Lymphocytic Infiltrates

scholarly journals High Expression of Ecto-Nucleotidases CD39 and CD73 in Human Endometrial Tumors

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Elisabet Aliagas ◽  
August Vidal ◽  
Laura Texidó ◽  
Jordi Ponce ◽  
Enric Condom ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endometrial Cancer ◽  
Genital Tract ◽  
Female Genital Tract ◽  
Tumor Grade ◽  
Type I ◽  
Type Ii ◽  
Extracellular Adenosine ◽  
Serous Tumors ◽  
Female Genital

One of the strategies used by tumors to evade immunosurveillance is the accumulation of extracellular adenosine, which has immunosupressive and tumor promoting effects. The study of the mechanisms leading to adenosine formation at the tumor interstitium are therefore of great interest in oncology. The dominant pathway generating extracellular adenosine in tumors is the dephosphorylation of ATP by ecto-nucleotidases. Two of these enzymes acting sequentially, CD39 and CD73, efficiently hydrolyze extracellular ATP to adenosine. They have been found to play a crucial role in a variety of tumors, but there were no data concerning endometrial cancer, the most frequent of the invasive tumors of the female genital tract. The aim of the present work is to study the expression of CD39 and CD73 in human endometrial cancer. We have analyzed protein and gene expression, as well as enzyme activity, in type I endometrioid adenocarcinomas and type II serous adenocarcinomas and their nonpathological endometrial counterparts. High levels of both enzymes were found in tumor samples, with significantly increased expression of CD39 in type II serous tumors, which also coincided with the higher tumor grade. Our results reinforce the involvement of the adenosinergic system in cancer, emphasizing the relevance of ecto-nucleotidases as emerging therapeutic targets in oncology.

EVALUATION OF MYOMETRIAL INVASION AND CERVICAL INVOLVEMENT IN TYPE I ENDOMETRIAL CANCER USING DIFFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING

2020 ◽  
pp. 4-6
Author(s):  
HARIYONO WINARTO ◽  
BRIAN PRIMA ARTHA ◽  
SAHAT B. MATONDANG ◽  
TANTRI HELLYANTI ◽  
ARIA KEKALIH
Keyword(s):  
Magnetic Resonance Imaging ◽  
Endometrial Cancer ◽  
Magnetic Resonance ◽  
Cancer Patients ◽  
Myometrial Invasion ◽  
Type I ◽  
Resonance Imaging ◽  
Diffusion Weighted ◽  
Weighted Magnetic Resonance Imaging ◽  
Cervical Involvement

Objective: Surgical procedure and adjuvant treatment of type I endometrial cancer were affected by some variables assessed preoperatively. Diffusion-weighted magnetic resonance imaging (DWI) is a promising modality in evaluating myometrial invasion and cervical involvement, investigating the diagnostic values of DWI in assessing myometrial invasion and cervical involvement. Methods: A cross-sectional study was conducted. This study involved all type I endometrial cancer patients in Dr. Cipto Mangunkusumo Hospital from April 2016 until April 2019. The depth of myometrial invasion and cervical involvement was examined using 1.5-T MR unit. The result was compared to the surgical pathologic findings as the reference standard. Results: 34 types I endometrial cancer patients were enrolled in this study. The sensitivity of DWI in evaluating myometrial invasion and cervical involvement in type I endometrial cancer was 94.12% and 57.14%, while the specificity was 64.71% and 92.59%, respectively. Conclusion: DWI can provide reliable prognostic variable information about the myometrial invasion and cervical involvement in the preoperative preparation of endometrial cancer patients.

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