Colo-rectal Cancer, Hereditary Diseases, Lynch Syndrome
Conditions
Keywords
Lynch Syndrom, Colorectal Cancer
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.
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_TESTdiagnostic 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
Sponsors
Izmir Ataturk Training and Research Hospital
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Lynch Syndrome Among Surgically Treated Colorectal Cancer Patients | Within 12 months following surgical resection and pathological assessment | 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. |
Outcome results
None listed