Frequency of Endometrial Cancer Precursors Associated with Lynch Syndrome

NCT05257057 | Completed

• 1 other identifier: 1403922-5
• Study Type: observational
• Target: 91
• Locations: 1 country
• Sites: 1

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.

Conditions

Lynch Syndrome; Endometrial Cancer; Endometrial Hyperplasia; Mismatch Repair Deficiency; Microsatellite Instability

Keywords

Lynch Syndrome; endometrial hyperplasia; endometrial cancer; immunohistochemistry; mismatch repair

Outcome Measures

Primary Outcomes (1)

• Lynch Syndrome Screen Positive Rate

  This is the rate of subjects who screen positive for Lynch Syndrome based on immunohistochemical staining

  2014-2022

Study Arms (1)

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

Interventions

Immunohistochemical staining DIAGNOSTIC_TEST

Immunohistochemistry will be performed on the endometrial tissue specimens

Endometrial hyperplasia

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• WellSpan Health: lead

Study Sites (1)

WellSpan

York, Pennsylvania, 17403, United States

Location

Related Publications (15)

• 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.

  PMID: 21205737 BACKGROUND

• 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.

  PMID: 24978665 BACKGROUND

• 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.

  PMID: 30115102 BACKGROUND

• 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.

  PMID: 23531335 BACKGROUND

• 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.

  PMID: 25437740 BACKGROUND

• 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.

  PMID: 4005805 BACKGROUND

• 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.

  PMID: 11054716 BACKGROUND

• 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.

  PMID: 25798423 BACKGROUND

• 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.

  PMID: 17630117 BACKGROUND

• 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.

  PMID: 23760948 BACKGROUND

• 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.

  PMID: 11956307 BACKGROUND

• 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.

  PMID: 24631699 BACKGROUND

• 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.

  PMID: 22865035 BACKGROUND

• 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.

  PMID: 14668545 BACKGROUND

• 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.

  PMID: 26807560 BACKGROUND

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.

MeSH Terms

Conditions

Colorectal Neoplasms, Hereditary Nonpolyposis; Endometrial Neoplasms; Endometrial Hyperplasia; Turcot syndrome; Microsatellite Instability

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genomic Instability; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Eav Lim, DO

  WellSpan Health-York Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 16, 2022
• First Posted: February 25, 2022
• Study Start: May 8, 2019
• Primary Completion: June 2, 2023
• Study Completion: June 2, 2023
• Last Updated: March 28, 2025

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)