Frequency of Endometrial Cancer Precursors Associated with Lynch Syndrome

NCT ID: NCT05257057

Last Updated: 2025-03-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

91 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-05-08

Study Completion Date

2023-06-02

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Lynch Syndrome Endometrial Cancer Endometrial Hyperplasia Mismatch Repair Deficiency Microsatellite Instability

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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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.

Immunohistochemical staining

Intervention Type DIAGNOSTIC_TEST

Immunohistochemistry will be performed on the endometrial tissue specimens

Interventions

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Immunohistochemical staining

Immunohistochemistry will be performed on the endometrial tissue specimens

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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WellSpan Health

OTHER

Sponsor Role lead

Responsible Party

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Eav Lim

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Eav Lim, DO

Role: PRINCIPAL_INVESTIGATOR

WellSpan Health-York Cancer Center

Locations

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WellSpan

York, Pennsylvania, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 21205737 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24978665 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30115102 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23531335 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25437740 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 4005805 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11054716 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25798423 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17630117 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23760948 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11956307 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24631699 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22865035 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14668545 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26807560 (View on PubMed)

Other Identifiers

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1403922-5

Identifier Type: -

Identifier Source: org_study_id

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