Lynch Syndrome in Colorectal Cancer Surgery

NCT ID: NCT06990633

Last Updated: 2025-05-25

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

NOT_YET_RECRUITING

Total Enrollment

180 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-07-01

Study Completion Date

2026-08-01

Brief Summary

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Study Design (Material and Methods)

This is a multicentre, prospective cohort and audit study conducted in Türkiye. The study aims to evaluate the incidence of Lynch syndrome among patients who undergo surgery for colorectal cancer in participating general surgery departments.

Over a 12-month period, patients undergoing surgery for histologically confirmed colorectal cancer at multiple tertiary hospitals across Türkiye will be enrolled. Postoperative pathological assessments will include immunohistochemical (IHC) analysis for mismatch repair (MMR) protein expression (MLH1, PMS2, MSH2, and MSH6).

In cases showing loss of MLH1 and PMS2 expression, BRAF mutation testing will be performed. If BRAF mutation is detected, MLH1 promoter methylation analysis will follow. A positive result in both tests will suggest a sporadic etiology, whereas the absence of both findings will lead to referral for germline genetic testing using next-generation sequencing (NGS) to investigate Lynch syndrome.

For patients with isolated MSH2 and/or MSH6 loss, direct referral to genetic testing will be carried out without BRAF or methylation testing.

Patients with intact MMR expression will be recorded as the MMR-proficient control group. Comparative analysis will be conducted between dMMR and MMR-proficient patients, including demographic characteristics (age, sex, family history of cancer), tumor staging, anatomical location, and presence of metastases.

The primary outcome is to determine the incidence of Lynch syndrome among surgically treated colorectal cancer patients in Türkiye and to identify clinical and pathological correlations.

Detailed Description

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Study Design (Material and Methods)

This is a multicentre, prospective cohort and audit study conducted in Türkiye. The study aims to evaluate the incidence of Lynch syndrome among patients who undergo surgery for colorectal cancer in participating general surgery departments.

Over a 12-month period, patients undergoing surgery for histologically confirmed colorectal cancer at multiple tertiary hospitals across Türkiye will be enrolled. Postoperative pathological assessments will include immunohistochemical (IHC) analysis for mismatch repair (MMR) protein expression (MLH1, PMS2, MSH2, and MSH6).

In cases showing loss of MLH1 and PMS2 expression, BRAF mutation testing will be performed. If BRAF mutation is detected, MLH1 promoter methylation analysis will follow. A positive result in both tests will suggest a sporadic etiology, whereas the absence of both findings will lead to referral for germline genetic testing using next-generation sequencing (NGS) to investigate Lynch syndrome.

For patients with isolated MSH2 and/or MSH6 loss, direct referral to genetic testing will be carried out without BRAF or methylation testing.

Patients with intact MMR expression will be recorded as the MMR-proficient control group. Comparative analysis will be conducted between dMMR and MMR-proficient patients, including demographic characteristics (age, sex, family history of cancer), tumor staging, anatomical location, and presence of metastases.

The primary outcome is to determine the incidence of Lynch syndrome among surgically treated colorectal cancer patients in Türkiye and to identify clinical and pathological correlations.

Conditions

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Colo-rectal Cancer Hereditary Diseases Lynch Syndrome

Study Design

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Observational Model Type

OTHER

Study Time Perspective

PROSPECTIVE

Study Groups

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dmmr

dmmr

diagnostic test

Intervention Type DIAGNOSTIC_TEST

Group 1: MMR-Proficient Group Label: MMR-Proficient

Description: Patients with normal expression of MMR proteins on IHC analysis. No indication for further genetic testing.

Type: Observational Group

Group 2: dMMR Group Label: dMMR

Description: Patients with loss of MMR protein expression (MLH1, PMS2, MSH2, or MSH6) on IHC. These patients will undergo further molecular or genetic analysis to evaluate for Lynch syndrome.

Type: Observational Group

mmr expression normal

mmr expression normal

No interventions assigned to this group

Interventions

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diagnostic test

Group 1: MMR-Proficient Group Label: MMR-Proficient

Description: Patients with normal expression of MMR proteins on IHC analysis. No indication for further genetic testing.

Type: Observational Group

Group 2: dMMR Group Label: dMMR

Description: Patients with loss of MMR protein expression (MLH1, PMS2, MSH2, or MSH6) on IHC. These patients will undergo further molecular or genetic analysis to evaluate for Lynch syndrome.

Type: Observational Group

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

Age 18 years or older

Histologically confirmed diagnosis of colorectal adenocarcinoma

Undergoing surgical resection at one of the participating general surgery departments

Availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue for MMR analysis

Consent to participate in the study and undergo genetic testing if indicated

Exclusion Criteria

Age below 18 years

Diagnosis other than colorectal adenocarcinoma

Incomplete or unavailable postoperative pathology results

Inadequate tissue samples for IHC analysis

Patients who decline participation in the study at any point

Patients who do not attend or refuse referral to genetic counseling after pathology results
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Izmir Ataturk Training and Research Hospital

OTHER

Sponsor Role lead

Responsible Party

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SAADET KOCA

md ftbs phd-c

Responsibility Role PRINCIPAL_INVESTIGATOR

Other Identifiers

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Hilal

Identifier Type: -

Identifier Source: org_study_id

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