Lynch Syndrome Can be Diagnosed Just From Somatic Mismatch Repair Mutation

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

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.

Study Overview

• Status: Unknown
• Conditions: Lynch Syndrome; Endometrial Cancer; Somatic Mutation; Cancer Gene Mutation
• Intervention / Treatment: Diagnostic test: Mismatch repair instability somatic and germline testing

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: ariel polonsky, MD; Phone Number: 5512276993; Email: arielpolonskymd@gmail.com
• Study Contact Backup: Name: Noah Goldman, MD; Email: ng510@njms.rutgers.edu

Study Locations

• United States
  • New Jersey
    • Jersey City, New Jersey, United States, 07302
      • Recruiting
      • Jersey City Medical Center
      • Contact: ariel polonsky, MD; Phone Number: 551-227-6993; Email: arielpolonskymd@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

The population includes female patients of all ages and races who are from a low socioeconomic background defined by the american psychological association.

These females usually reside in underserved area. All the patients are diagnosed with endometrial endometrioid adenocarcinoma via tissue biopsy.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: RWJ Barnabas Health at Jersey City Medical Center

Publications and helpful links

General Publications

• 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.
• 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. doi: 10.1097/01.pas.0000213428.61374.06.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2019
• Primary Completion (Anticipated): December 30, 2020
• Study Completion (Anticipated): June 30, 2021

Study Registration Dates

• First Submitted: August 3, 2020
• First Submitted That Met QC Criteria: August 13, 2020
• First Posted (Actual): August 17, 2020

Study Record Updates

• Last Update Posted (Actual): August 18, 2020
• Last Update Submitted That Met QC Criteria: August 15, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Metabolic Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Disease; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Genetic Diseases, Inborn; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Neoplastic Syndromes, Hereditary; DNA Repair-Deficiency Disorders; Syndrome; Colorectal Neoplasms, Hereditary Nonpolyposis; Endometrial Neoplasms
• Other Study ID Numbers: 1272883

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No