Lynch Syndrome Can be Diagnosed Just From Somatic Mismatch Repair Mutation

Endometrial Cancer Clinical Trial

Official title:

Correlation Between Somatic Mismatch Repair Instability and Germline Mismatch Repair Instability, in Low Socioeconomic Background Population Diagnosed With Endometrial Endometrioid Adenocarcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04516083
• Other study ID #: 1272883
• Status: Recruiting
• Start date: December 21, 2019
• Est. completion date: June 30, 2021

Study information

• Verified date: August 2020
• Source: RWJ Barnabas Health at Jersey City Medical Center
• Contact: Ariel Polonsky, MD
• Phone: 5512276993
• Email: arielpolonskymd[@]gmail.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The objective of the study is the provide proof of high correlation between somatic and germline mismatch repair instability. This correlation is specifically researched in an area where patients have less access to cancer education and genetic testing for various reasons such as lack of insurance and general accessibility.

The study concentrates on early diagnosis of Lynch syndrome. Lynch syndrome is usually diagnosed from a blood test resulting in a mutation of one of the mismatch repair genes. Those are MLH1, MSH2, MSH 6, PMS2. A mutation in one of these genes creates a mismatch repair instability,hence higher incidence of cancers in specific organ groups. Amongst these organs are the Uterus, Ovaries, Upper genitourinary system, Pancreas and GI system.

The most common endometrial carcinoma which is found in Lynch syndrome is of endometrioid histology. Most patients with known germline mismatch repair instability, have the same somatic mutation. Our study is looking into correlating somatic mutation to germline mutation.

By doing so, patients diagnosed with somatic mismatch repair instability will be also diagnosed with lynch syndrome without germline genetic testing.

Screening programs will be utilized earlier and preventive procedures offered.

Due to less access to educational programs, genetic counseling and testing in underserved areas, patients are sometimes lost to follow up. Our study seeks to prove high correlation between somatic and germline mutations and by doing so, patient will be diagnosed with Lynch syndrome straight after endometrial cancer staging. As a result, increased compliance will be expected and patients will be offered the recommended preventative surgeries and screening protocols.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 30, 2021
• Est. primary completion date: December 30, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

Inclusion Criteria:

Underserved areas. Diagnosis of endometrial endometrioid carcinoma. Low socioeconomic status. Positive mismatch repair staining. All races. All ages. All cancer grades. All cancer stages .

Exclusion Criteria:

Diagnosis of type 2 endometrial carcinoma. Cancer diagnosis other than Endometrial. No mismatch repair genes mutation. High socioeconomic status.

Related Conditions & MeSH terms

• Cancer Gene Mutation
• Colorectal Neoplasms, Hereditary Nonpolyposis
• Endometrial Cancer
• Endometrial Neoplasms
• Lynch Syndrome
• Somatic Mutation
• Syndrome

Intervention

Diagnostic Test:
• Mismatch repair instability somatic and germline testing
Each Endometrial Endometrioid adenocarcinoma is routinely stained for MMR mutation to seek for tumor genetic instability. If stains positive, the patient is called in for genetic blood testing to look for the same mutation in the germline.

Locations

Country	Name	City	State
United States	Jersey city medical center	Jersey City	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
RWJ Barnabas Health at Jersey City Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (3)

Chu MM, Liu SS, Tam KF, Ip PP, Cheung AN, Ngan HY. The Significance of Mismatch Repair Deficiency in Young Patients With Endometrial Cancer. Int J Gynecol Pathol. 2015 Sep;34(5):403-10. doi: 10.1097/PGP.0000000000000174. — View Citation

Kahn RM, Gordhandas S, Maddy BP, Baltich Nelson B, Askin G, Christos PJ, Caputo TA, Chapman-Davis E, Holcomb K, Frey MK. Universal endometrial cancer tumor typing: How much has immunohistochemistry, microsatellite instability, and MLH1 methylation improved the diagnosis of Lynch syndrome across the population? Cancer. 2019 Sep 15;125(18):3172-3183. doi: 10.1002/cncr.32203. Epub 2019 May 31. Review. — View Citation

Modica I, Soslow RA, Black D, Tornos C, Kauff N, Shia J. Utility of immunohistochemistry in predicting microsatellite instability in endometrial carcinoma. Am J Surg Pathol. 2007 May;31(5):744-51. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients who have a somatic mutation at the same time as a germline mutation	Resected tissue during endometrial staging will be immunohistochemically stained for MMR mutation.; Patient blood test will be checked for MMR gene mutation; Linear regression curve will be constructed to evaluate the correlation between somatic and germline mutation.	Through study completion, an average of 18 months