Literature DB >> 17513808

Microsatellite instability and epigenetic inactivation of MLH1 and outcome of patients with endometrial carcinomas of the endometrioid type.

Israel Zighelboim1, Paul J Goodfellow, Feng Gao, Randall K Gibb, Matthew A Powell, Janet S Rader, David G Mutch.   

Abstract

PURPOSE: Most studies of microsatellite instability (MSI) and outcomes in endometrial cancer patients have included varied histologic subtypes. Nonetheless, MSI occurs almost exclusively in endometrioid tumors. The impact of MSI on outcomes in patients with endometrial cancer is controversial. We sought to determine whether MSI and MLH1 methylation are associated with clinicopathologic variables and survival outcomes in a large series of patients with endometrial carcinomas of the endometrioid type. PATIENTS AND METHODS: Tumor samples, blood, and clinicopathologic data were prospectively collected and analyzed for 446 patients with endometrioid carcinomas. MSI was determined using five National Cancer Institute (NCI) consensus panel markers, and the methylation status of the MLH1 promoter was determined by combined bisulfite restriction analysis (COBRA). Associations with clinicopathologic variables and survival outcomes were evaluated.
RESULTS: MSI was identified in 147 cases (33%). MSI was associated with higher International Federation of Gynecology and Obstetrics (FIGO) grade (P < .0001). MSI+ tumors without MLH1 methylation were associated with younger age (P < .001). MSI was not associated with overall survival (OS; hazard ratio [HR], 1.011; 95% CI, 0.688 to 1.484; P = .96) or disease-free survival (DFS; HR 0.951; 95% CI, 0.554 to 1.635; P = .86). The combined MSI/MLH1 methylation status (treating MSI- as the reference) did not predict OS (MSI+/MLH1-U: HR, 0.62; 95% CI, 0.27 to 1.44; P = .26; MSI+/MLH1-M: HR, 0.95; 95% CI, 0.62 to 1.46; P = .82) or DFS (MSI+/MLH1-U: HR, 0.51; 95% CI, 0.22 to 1.19; P = .12; MSI+/MLH1-M: HR, 0.93; 95% CI, 0.62 to 1.40; P = .72).
CONCLUSION: MSI is not associated with survival in patients with endometrioid endometrial cancer.

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Year:  2007        PMID: 17513808     DOI: 10.1200/JCO.2006.08.2107

Source DB:  PubMed          Journal:  J Clin Oncol        ISSN: 0732-183X            Impact factor:   44.544


  67 in total

1.  DICER1 expression and outcomes in endometrioid endometrial adenocarcinoma.

Authors:  Israel Zighelboim; Andrew J Reinhart; Feng Gao; Amy P Schmidt; David G Mutch; Premal H Thaker; Paul J Goodfellow
Journal:  Cancer       Date:  2010-11-08       Impact factor: 6.860

2.  SOX11 hypermethylation as a tumor biomarker in endometrial cancer.

Authors:  Tianjiao Shan; Denise S Uyar; Li-Shu Wang; David G Mutch; Tim H-M Huang; Janet S Rader; Xiugui Sheng; Yi-Wen Huang
Journal:  Biochimie       Date:  2019-03-29       Impact factor: 4.079

Review 3.  The emerging genomic landscape of endometrial cancer.

Authors:  Matthieu Le Gallo; Daphne W Bell
Journal:  Clin Chem       Date:  2013-10-29       Impact factor: 8.327

4.  ERM/ETV5 and RUNX1/AML1 expression in endometrioid adenocarcinomas of endometrium and association with neoplastic progression.

Authors:  Vanessa Paiva Leite de Sousa; Claudia Bessa Pereira Chaves; Janina Ferreira Loureiro Huguenin; Fábio Carvalho de Barros Moreira; Bruno Souza Bianchi de Reis; Leila Chimelli; Anke Bergmann; Tatiana de Almeida Simão; Luis Felipe Ribeiro Pinto
Journal:  Cancer Biol Ther       Date:  2014-04-22       Impact factor: 4.742

5.  Epigenetic silencing of MLH1 in endometrial cancers is associated with larger tumor volume, increased rate of lymph node positivity and reduced recurrence-free survival.

Authors:  Casey M Cosgrove; David E Cohn; Heather Hampel; Wendy L Frankel; Dan Jones; Joseph P McElroy; Adrian A Suarez; Weiqiang Zhao; Wei Chen; Ritu Salani; Larry J Copeland; David M O'Malley; Jeffrey M Fowler; Ahmet Yilmaz; Alexis S Chassen; Rachel Pearlman; Paul J Goodfellow; Floor J Backes
Journal:  Gynecol Oncol       Date:  2017-07-11       Impact factor: 5.482

Review 6.  Non-Coding RNAs in Endometrial Physiopathology.

Authors:  Alessandro La Ferlita; Rosalia Battaglia; Francesca Andronico; Salvatore Caruso; Antonio Cianci; Michele Purrello; Cinzia Di Pietro
Journal:  Int J Mol Sci       Date:  2018-07-20       Impact factor: 5.923

Review 7.  Endometrial cancer and Lynch syndrome: clinical and pathologic considerations.

Authors:  Larissa A Meyer; Russell R Broaddus; Karen H Lu
Journal:  Cancer Control       Date:  2009-01       Impact factor: 3.302

8.  Risk factors for developing endometrial cancer after benign endometrial sampling.

Authors:  Michelle L Torres; Amy L Weaver; Sanjeev Kumar; Stefano Uccella; Abimbola O Famuyide; William A Cliby; Sean C Dowdy; Bobbie S Gostout; Andrea Mariani
Journal:  Obstet Gynecol       Date:  2012-11       Impact factor: 7.661

9.  Microsatellite instability predicts clinical outcome in radiation-treated endometrioid endometrial cancer.

Authors:  Cristina Bilbao; Pedro Carlos Lara; Raquel Ramírez; Luis Alberto Henríquez-Hernández; Germán Rodríguez; Orlando Falcón; Laureano León; Manuel Perucho; Bonifacio Nicolás Díaz-Chico; Juan Carlos Díaz-Chico
Journal:  Int J Radiat Oncol Biol Phys       Date:  2010-01-01       Impact factor: 7.038

10.  Estrogen receptor-alpha as a predictive biomarker in endometrioid endometrial cancer.

Authors:  Floor J Backes; Christopher J Walker; Paul J Goodfellow; Erinn M Hade; Garima Agarwal; David Mutch; David E Cohn; Adrian A Suarez
Journal:  Gynecol Oncol       Date:  2016-03-10       Impact factor: 5.482

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