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Lynch Syndrome in Colorectal Cancer Surgery

Observational Colo-rectal Cancer Hereditary Diseases Lynch Syndrome

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: diagnostic test.
Who it may be relevant to
Registry conditions: Colo-rectal Cancer, Hereditary Diseases, Lynch Syndrome. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Center list to be confirmed — check the primary protocol.
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Official title

LYNX STUDY: Lynch Syndrome in Colorectal Cancer Surgery - A Multicentre, Prospective Cohort Study

Overview

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

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.

Interventions

  • Diagnostic test 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

Primary outcome measures

  • Incidence of Lynch Syndrome Among Surgically Treated Colorectal Cancer Patients [Time frame: Within 12 months following surgical resection and pathological assessment]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model
Other

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06990633 · Hilal

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗