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.

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.

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

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.