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Molecular markers in recurrent stage I, grade 1 endometrioid endometrial cancers.
Gynecol Oncol. 2019 06; 153(3):517-520.GO

Abstract

OBJECTIVES

Stage I, grade 1 endometrial cancers have low recurrence rates and often do not receive adjuvant therapy. We compared recurrent cases to matched non-recurrent controls to evaluate for molecular markers associated with higher risk of recurrence.

METHODS

A case-control study including all cases of recurrent stage I, grade 1 endometrioid endometrial cancer at one institution in a ten-year period. Cases were matched to controls by age, BMI, weight and stage. Molecular testing and immunohistochemistry were performed on archival tumor specimens: microsatellite instability (MSI-H), mismatch repair status, POLE mutational status, and next-generation sequencing.

RESULTS

15 stage I, grade 1 endometrial cancer cases with recurrent disease and available tumor specimens were identified. CTNNB1 and MSI-H were present at significantly higher rates in cases than controls (CTNNB1 60% vs. 28%, OR 3.9, 95%CI 1.1-14.7, p = 0.04 and MSI-H 53% vs. 21%, OR 4.4, 95%CI 1.1-17.0, p = 0.03). POLE mutations were found in 0% of cases vs. 7% of controls (p = 0.54). Among specimens demonstrating microsatellite stability (MSS), 100% of cases vs. 26% of controls had CTNNB1 mutations (p < 0.001). CTNNB1 wild type tumors were MSI-H in 100% of cases vs. 19% of controls (p < 0.001).

CONCLUSIONS

Compared to controls, CTNNB1 mutation is present at significantly higher rates in recurrent stage I, grade 1 endometrial cancers and is found most commonly in MSS tumors. MSI-H is also present at significantly higher rates in recurrent cases. These markers may be useful for prognostic risk stratification and adjuvant therapy decision-making in this otherwise low-risk population.

Authors+Show Affiliations

University of Colorado Denver, Department of Obstetrics and Gynecology, Aurora, CO, United States of America. Electronic address: marisa.moroney@ucdenver.edu.University of Colorado Denver Aurora, Department of Pathology, CO, United States of America.University of Colorado Denver Aurora, Department of Pathology, CO, United States of America.University of Colorado Denver, Department of Obstetrics and Gynecology, Aurora, CO, United States of America.University of Colorado Denver, Department of Obstetrics and Gynecology, Aurora, CO, United States of America; University of Colorado Denver Aurora, Department of Pathology, CO, United States of America.University of Colorado Denver Aurora, Department of Pathology, CO, United States of America.University of Colorado Denver Aurora, Department of Radiation Oncology, CO, United States of America.University of Colorado Denver Aurora, Department of Gynecologic Oncology, CO, United States of America.University of Colorado Denver Aurora, Department of Gynecologic Oncology, CO, United States of America.University of Colorado Denver Aurora, Department of Gynecologic Oncology, CO, United States of America.University of Colorado Denver Aurora, Department of Gynecologic Oncology, CO, United States of America.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30910249

Citation

Moroney, Marisa R., et al. "Molecular Markers in Recurrent Stage I, Grade 1 Endometrioid Endometrial Cancers." Gynecologic Oncology, vol. 153, no. 3, 2019, pp. 517-520.
Moroney MR, Davies KD, Wilberger AC, et al. Molecular markers in recurrent stage I, grade 1 endometrioid endometrial cancers. Gynecol Oncol. 2019;153(3):517-520.
Moroney, M. R., Davies, K. D., Wilberger, A. C., Sheeder, J., Post, M. D., Berning, A. A., Fisher, C., Lefkowits, C., Guntupalli, S. R., Behbakht, K., & Corr, B. R. (2019). Molecular markers in recurrent stage I, grade 1 endometrioid endometrial cancers. Gynecologic Oncology, 153(3), 517-520. https://doi.org/10.1016/j.ygyno.2019.03.100
Moroney MR, et al. Molecular Markers in Recurrent Stage I, Grade 1 Endometrioid Endometrial Cancers. Gynecol Oncol. 2019;153(3):517-520. PubMed PMID: 30910249.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular markers in recurrent stage I, grade 1 endometrioid endometrial cancers. AU - Moroney,Marisa R, AU - Davies,Kurtis D, AU - Wilberger,Adam C, AU - Sheeder,Jeanelle, AU - Post,Miriam D, AU - Berning,Amber A, AU - Fisher,Christine, AU - Lefkowits,Carolyn, AU - Guntupalli,Saketh R, AU - Behbakht,Kian, AU - Corr,Bradley R, Y1 - 2019/03/22/ PY - 2019/01/11/received PY - 2019/03/08/revised PY - 2019/03/10/accepted PY - 2019/3/27/pubmed PY - 2019/8/14/medline PY - 2019/3/27/entrez KW - Endometrial cancer KW - Molecular testing KW - Risk-stratification SP - 517 EP - 520 JF - Gynecologic oncology JO - Gynecol Oncol VL - 153 IS - 3 N2 - OBJECTIVES: Stage I, grade 1 endometrial cancers have low recurrence rates and often do not receive adjuvant therapy. We compared recurrent cases to matched non-recurrent controls to evaluate for molecular markers associated with higher risk of recurrence. METHODS: A case-control study including all cases of recurrent stage I, grade 1 endometrioid endometrial cancer at one institution in a ten-year period. Cases were matched to controls by age, BMI, weight and stage. Molecular testing and immunohistochemistry were performed on archival tumor specimens: microsatellite instability (MSI-H), mismatch repair status, POLE mutational status, and next-generation sequencing. RESULTS: 15 stage I, grade 1 endometrial cancer cases with recurrent disease and available tumor specimens were identified. CTNNB1 and MSI-H were present at significantly higher rates in cases than controls (CTNNB1 60% vs. 28%, OR 3.9, 95%CI 1.1-14.7, p = 0.04 and MSI-H 53% vs. 21%, OR 4.4, 95%CI 1.1-17.0, p = 0.03). POLE mutations were found in 0% of cases vs. 7% of controls (p = 0.54). Among specimens demonstrating microsatellite stability (MSS), 100% of cases vs. 26% of controls had CTNNB1 mutations (p < 0.001). CTNNB1 wild type tumors were MSI-H in 100% of cases vs. 19% of controls (p < 0.001). CONCLUSIONS: Compared to controls, CTNNB1 mutation is present at significantly higher rates in recurrent stage I, grade 1 endometrial cancers and is found most commonly in MSS tumors. MSI-H is also present at significantly higher rates in recurrent cases. These markers may be useful for prognostic risk stratification and adjuvant therapy decision-making in this otherwise low-risk population. SN - 1095-6859 UR - https://www.unboundmedicine.com/medline/citation/30910249/Molecular_markers_in_recurrent_stage_I_grade_1_endometrioid_endometrial_cancers_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0090-8258(19)30273-2 DB - PRIME DP - Unbound Medicine ER -