Frequency of Endometrial Cancer Precursors Associated With Lynch Syndrome

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ClinicalTrials.gov Identifier: NCT05257057

Recruitment Status : Recruiting

First Posted : February 25, 2022

Last Update Posted : June 6, 2022

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View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Eav Lim, WellSpan Health

Study Description

Brief Summary:

Given that there is a significant prevalence of Lynch syndrome among patients with endometrial cancer (about 5% of patients with endometrial cancer), and given there is a known risk of endometrial cancer among patients with endometrial hyperplasia (40% risk of pre-existing occult cancer with endometrial intraepithelial neoplasia), it is hypothesized that a diagnosis of endometrial hyperplasia may herald on-going risk of harboring a Lynch Syndrome gene mutation.

The purpose of this study is to examine endometrial hyperplasia specimens and compare the frequency of Lynch Syndrome gene mutations between endometrial hyperplasia and endometrial cancer subjects. This will provide a rationale and opportunity for earlier screening, and reduce colon cancer morbidity and mortality secondary to the Lynch syndrome gene.

Condition or disease	Intervention/treatment
Lynch Syndrome Endometrial Cancer Endometrial Hyperplasia Mismatch Repair Deficiency Microsatellite Instability	Diagnostic Test: Immunohistochemical staining

Detailed Description:

This is an observational cohort study. Tissue specimens obtained that have been labeled with the diagnosis of endometrial hyperplasia will be identified and their chart reviewed for demographic date of age, race, body mass index, and co-morbidities. The specimen will then be tested via immunohistochemistry for the mismatch repair proteins MLH1, PMS2, MSH2, or MSH 6. Their absence is indicative of Lynch Syndrome. Statistical analysis will then be performed to compare the incidence of Lynch syndrome in endometrial hyperplasia with Lynch Syndrome in endometrial cancer.

Study Design

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Study Type :	Observational
Estimated Enrollment :	150 participants
Observational Model:	Cohort
Time Perspective:	Retrospective
Official Title:	Frequency of Endometrial Cancer Precursors Associated With Lynch Syndrome
Actual Study Start Date :	May 8, 2019
Estimated Primary Completion Date :	December 2022
Estimated Study Completion Date :	January 2023

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Constitutional mismatch repair deficiency syndrome Lynch syndrome

Genetic and Rare Diseases Information Center resources: Turcot Syndrome

U.S. FDA Resources

Groups and Cohorts

Group/Cohort	Intervention/treatment
Endometrial hyperplasia These are patients with a diagnosis of endometrial hyperplasia at WellSpan in the study time frame diagnosed via endometrial biopsy, dilation and curettage, or hysterectomy.	Diagnostic Test: Immunohistochemical staining Immunohistochemistry will be performed on the endometrial tissue specimens

Outcome Measures

Primary Outcome Measures :

Lynch Syndrome Screen Positive Rate [ Time Frame: 2014-2022 ]
This is the rate of subjects who screen positive for Lynch Syndrome based on immunohistochemical staining

Biospecimen Retention: Samples With DNA

No new biospecimens are retained. The biospecimens referenced are those that were already collected for tissue diagnosis of endometrial hyperplasia: endometrial biopsies, curettage specimens, and hysterectomy specimens. These are kept routinely in the pathology department on microscope slides post-procedure per hospital policy.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 99 Years (Adult, Older Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

Patients who underwent tissue sampling of any type and received a pathologic diagnosis of endometrial hyperplasia at WellSpan from 2014-2022.

Criteria

Inclusion Criteria:

Appropriate specimen, hysterectomy or biopsy with final labeled diagnosis of endometrial hyperplasia of any grade

Exclusion Criteria:

Any specimen that is later associated with endometrial cancer in subsequent pathology exam

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05257057

Contacts

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Contact: Eav Lim, DO	(717) 851-6120	elim@wellspan.org
Contact: Kathryn Kennedy, MD	7178516120	kkennedy15@wellspan.org

Locations

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United States, Pennsylvania
WellSpan	Recruiting
York, Pennsylvania, United States, 17403
Contact: Eav Lim, DO 717-741-8100 elim@wellspan.org

Sponsors and Collaborators

WellSpan Health

Investigators

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Principal Investigator:	Eav Lim, DO	WellSpan Health-York Cancer Center

More Information

Publications:

Hampel H, de la Chapelle A. The search for unaffected individuals with Lynch syndrome: do the ends justify the means? Cancer Prev Res (Phila). 2011 Jan;4(1):1-5. doi: 10.1158/1940-6207.CAPR-10-0345.

Sehgal R, Sheahan K, O'Connell PR, Hanly AM, Martin ST, Winter DC. Lynch syndrome: an updated review. Genes (Basel). 2014 Jun 27;5(3):497-507. doi: 10.3390/genes5030497.

Ryan NAJ, Blake D, Cabrera-Dandy M, Glaire MA, Evans DG, Crosbie EJ. The prevalence of Lynch syndrome in women with endometrial cancer: a systematic review protocol. Syst Rev. 2018 Aug 16;7(1):121. doi: 10.1186/s13643-018-0792-8.

Wang Y, Wang Y, Li J, Cragun J, Hatch K, Chambers SK, Zheng W. Lynch syndrome related endometrial cancer: clinical significance beyond the endometrium. J Hematol Oncol. 2013 Mar 25;6:22. doi: 10.1186/1756-8722-6-22.

ACOG Practice Bulletin No. 147: Lynch syndrome. Obstet Gynecol. 2014 Nov;124(5):1042-1054. doi: 10.1097/01.AOG.0000456325.50739.72. No abstract available. Erratum In: Obstet Gynecol. 2022 Apr 1;139(4):696.

Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia. A long-term study of "untreated" hyperplasia in 170 patients. Cancer. 1985 Jul 15;56(2):403-12. doi: 10.1002/1097-0142(19850715)56:23.0.co;2-x.

de Leeuw WJ, Dierssen J, Vasen HF, Wijnen JT, Kenter GG, Meijers-Heijboer H, Brocker-Vriends A, Stormorken A, Moller P, Menko F, Cornelisse CJ, Morreau H. Prediction of a mismatch repair gene defect by microsatellite instability and immunohistochemical analysis in endometrial tumours from HNPCC patients. J Pathol. 2000 Nov;192(3):328-35. doi: 10.1002/1096-9896(2000)9999:99993.0.CO;2-2.

Han SJ, Kim MK. Clinical significance of mismatch repair genes immunohistochemical expression of complex endometrial hyperplasia. Obstet Gynecol Sci. 2015 Mar;58(2):106-11. doi: 10.5468/ogs.2015.58.2.106. Epub 2015 Mar 16.

Horn LC, Meinel A, Handzel R, Einenkel J. Histopathology of endometrial hyperplasia and endometrial carcinoma: an update. Ann Diagn Pathol. 2007 Aug;11(4):297-311. doi: 10.1016/j.anndiagpath.2007.05.002.

Huang M, Djordjevic B, Yates MS, Urbauer D, Sun C, Burzawa J, Daniels M, Westin SN, Broaddus R, Lu K. Molecular pathogenesis of endometrial cancers in patients with Lynch syndrome. Cancer. 2013 Aug 15;119(16):3027-33. doi: 10.1002/cncr.28152. Epub 2013 Jun 12.

Ichikawa Y, Tsunoda H, Takano K, Oki A, Yoshikawa H. Microsatellite instability and immunohistochemical analysis of MLH1 and MSH2 in normal endometrium, endometrial hyperplasia and endometrial cancer from a hereditary nonpolyposis colorectal cancer patient. Jpn J Clin Oncol. 2002 Mar;32(3):110-2. doi: 10.1093/jjco/hyf026.

Ketabi Z, Gerdes AM, Mosgaard B, Ladelund S, Bernstein I. The results of gynecologic surveillance in families with hereditary nonpolyposis colorectal cancer. Gynecol Oncol. 2014 Jun;133(3):526-30. doi: 10.1016/j.ygyno.2014.03.012. Epub 2014 Mar 13.

Manchanda R, Saridogan E, Abdelraheim A, Johnson M, Rosenthal AN, Benjamin E, Brunell C, Side L, Gessler S, Jacobs I, Menon U. Annual outpatient hysteroscopy and endometrial sampling (OHES) in HNPCC/Lynch syndrome (LS). Arch Gynecol Obstet. 2012 Dec;286(6):1555-62. doi: 10.1007/s00404-012-2492-2. Epub 2012 Aug 4.

Sutter C, Dallenbach-Hellweg G, Schmidt D, Baehring J, Bielau S, von Knebel Doeberitz M, Gebert J. Molecular analysis of endometrial hyperplasia in HNPCC-suspicious patients may predict progression to endometrial carcinoma. Int J Gynecol Pathol. 2004 Jan;23(1):18-25. doi: 10.1097/01.pgp.0000101085.35393.4a.

Vierkoetter KR, Kagami LA, Ahn HJ, Shimizu DM, Terada KY. Loss of Mismatch Repair Protein Expression in Unselected Endometrial Adenocarcinoma Precursor Lesions. Int J Gynecol Cancer. 2016 Feb;26(2):228-32. doi: 10.1097/IGC.0000000000000606.

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Responsible Party:	Eav Lim, Principal Investigator, WellSpan Health
ClinicalTrials.gov Identifier:	NCT05257057
Other Study ID Numbers:	1403922-5
First Posted:	February 25, 2022 Key Record Dates
Last Update Posted:	June 6, 2022
Last Verified:	June 2022

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Eav Lim, WellSpan Health:


Lynch Syndrome endometrial hyperplasia endometrial cancer immunohistochemistry mismatch repair

Additional relevant MeSH terms:

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Endometrial Neoplasms Colorectal Neoplasms, Hereditary Nonpolyposis Endometrial Hyperplasia Syndrome Hyperplasia Microsatellite Instability Disease Pathologic Processes Uterine Neoplasms Genital Neoplasms, Female Urogenital Neoplasms Neoplasms by Site Neoplasms Uterine Diseases	Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplastic Syndromes, Hereditary Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Genetic Diseases, Inborn DNA Repair-Deficiency Disorders Metabolic Diseases Genomic Instability

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