Lynch Syndrome in Colorectal Cancer Surgery

NCT06990633 | Not Yet Recruiting

• 1 other identifier: Hilal
• Study Type: observational
• Target: 180
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Colo-rectal Cancer; Hereditary Diseases; Lynch Syndrome

Keywords

Lynch Syndrom, Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of Lynch Syndrome Among Surgically Treated Colorectal Cancer Patients

  The primary outcome is to determine the incidence of Lynch syndrome in patients who undergo surgery for colorectal cancer. The diagnosis will be based on initial immunohistochemical (IHC) analysis of MMR protein expression (MLH1, PMS2, MSH2, MSH6), followed by molecular and germline testing (BRAF mutation, MLH1 promoter methylation, and next-generation sequencing) when indicated.

  Within 12 months following surgical resection and pathological assessment

Study Arms (2)

dmmr

dmmr

Diagnostic Test: diagnostic test

mmr expression normal

mmr expression normal

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

dmmr

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population consists of adult patients (≥18 years) who undergo surgical resection for histologically confirmed colorectal adenocarcinoma at tertiary hospitals in Türkiye. Participants will include both elective and emergency surgical cases. All patients will have their tumor samples evaluated for MMR protein expression by immunohistochemistry. Patients with abnormal MMR expression will undergo further genetic testing. The population will represent a real-world surgical cohort, including both hereditary and sporadic colorectal cancer cases.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Izmir Ataturk Training and Research Hospital: lead

Biospecimen

Retention: SAMPLES WITH DNA

Types of Specimens: Formalin-fixed, paraffin-embedded (FFPE) tumor tissue obtained from surgical resection. Peripheral blood samples for germline DNA extraction. Time of Collection: Tumor tissue will be collected intraoperatively. Blood samples will be collected postoperatively at the time of referral for genetic testing. Purpose of Analysis: Tumor tissue will undergo IHC for MMR protein expression. Based on IHC results, additional analyses may include BRAF mutation and MLH1 promoter methylation. Blood-derived germline DNA will be analyzed via next-generation sequencing (NGS) to detect pathogenic variants associated with Lynch syndrome. Storage and Handling: FFPE blocks will be stored in hospital pathology units. Blood samples for DNA extraction will be processed and stored according to standard protocols in certified genetic laboratories. Location: Specimens will be collected from multiple surgical centers across Türkiye.

MeSH Terms

Conditions

Colonic Neoplasms; Genetic Diseases, Inborn; Colorectal Neoplasms, Hereditary Nonpolyposis; Colorectal Neoplasms

Interventions

Diagnostic Tests, Routine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neoplastic Syndromes, Hereditary; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Techniques and Procedures; Diagnosis

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: md ftbs phd-c

Study Record Dates

• First Submitted: May 17, 2025
• First Posted: May 25, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: May 25, 2025

Record last verified: 2025-02