Lynch syndrome association and clinicopathological features in early-onset colorectal cancers: A single-center retrospective study

Abstract

BACKGROUND

Hereditary factors are more prevalent in early-onset colorectal cancers (EOCRC) etiology. Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome that results from mutations in DNA mismatch repair (MMR) genes. This phenomenon is defined as microsatellite instability (MSI). Immunohistochemistry (IHC) is a widely used, practical, and cost-effective method for the screening of MSI. However, using IHC alone may be insufficient to identify patients with MSI and LS.

AIM

To determine the clinicopathological features in EOCRC, IHC performance, and the frequency of genetic testing for EOCRC patients.

METHODS

A retrospective review was conducted on patients with CRC aged ≤ 50 years who underwent surgery at our center between January 2014 and July 2021. MMR proteins were screened using IHC. Of the 131 patients included, IHC was performed on 130. Patients were classified as MSI or microsatellite-stable (MSS), and their features were compared. Additionally, data from patients who received genetic counseling were analyzed.

RESULTS

Thirty patients with MSI were designated as group 1, whereas 100 with MSS were defined as group 2. The mean age in group 1 was the lowest (median age: 42 vs 46, P < 0.05). Group 1 exhibited a higher frequency of tumors in the right colon and a lower frequency in the rectum. Lymph node involvement and distant metastases were less common in group 1, and in group 2, tumors were generally diagnosed at a more advanced stage. Genetic testing was performed in 53 patients (40%), with a definitive LS diagnosis established in 13/17 patients (76.4%) in group 1 and 1/36 (2.7%) patients in group 2, resulting in a total of 14 patients (26.4%) with confirmed LS.

CONCLUSION

MSI tumors show a better prognosis. IHC is very effective for screening MSI, but may not be sufficient alone. Low genetic counseling rates highlight the need for hospital-based surveillance programs.

Keywords: Early-onset colorectal cancer; Immunohistochemistry; Lynch syndrome; Microsatellite instability; Mismatch repair

Core Tip: Lynch syndrome (LS) results from microsatellite instability (MSI). Immunohistochemistry (IHC) is a cost-effective and practical method for MSI screening. This retrospective study evaluated clinicopathological features of MSI and microsatellite-stable (MSS) tumors in early-onset colorectal cancer patients between 2014 and 2021. MSI tumors were linked to younger age, right-sided location, and fewer metastases. Genetic testing confirmed LS in 76.4% of MSI and 2.8% of MSS cases based on IHC. However, 59.5% of patients did not receive genetic counseling. While IHC is useful for MSI detection, it may not be sufficient alone. Low counseling rates emphasize the need for hospital-based surveillance programs.