PROGRAMMED DEATH LIGAND-1 AND MUTL HOMOLOG-1 EXPRESSION IN COLORECTAL CANCER AND ITS CORRELATION WITH CLINICOPATHOLOGICAL PARAMETERS

Abstract

Background: Programmed death-ligand 1 (PD-L1) expression in colorectal cancer (CRC) has garnered significant attention due to its implications for immunotherapy and patient prognosis. PD-L1, a transmembrane protein, performs a crucial part in the immune system’s ability to regulate the balance between T cell activation and tolerance. In the context of CRC, PD-L1 expression can result in the inhibition of anti-tumor immune responses, allowing cancer cells to evade immune surveillance. Microsatellite instability (MSI) is a state defined by the accumulation of brief mutations; repetitive DNA sequences known as microsatellites. This condition results from defects in the DNA mismatch repair (MMR) system, which normally corrects errors that occur during DNA replication. MSI is a hallmark of a subset of CRCs and is connected to distinct clinical and pathological features, including a better response to certain immunotherapies. Aim of the study: 1. To determine the expression of Programmed Death Ligand-1(PD-L1) in colorectal carcinomas. 2. To determine the expression of MutL Homolog-1 (MLH-1) for Microsatellite instability status in colorectal carcinomas. 3. To determine the association of PD- L1 and MLH-1 expression with clinic pathological parameters of colorectal carcinoma. Materials and Methods: The study was conducted in Department of Pathology in Collaboration with Department of General Surgery, Sri Devaraj Urs Medical College attached to RL Jalappa Hospital and Research centre, Tamaka, Kolar during the period of August 2022 to May 2024. The study includes 76 cases of colorectal carcinoma diagnosed by histopathology. IHC was performed using the antibodies against PDL1. Expression of PDL1 was documented and analysed. Statistical analysis was performed using Chi-square test or Fischers exact test. A p value of less than 0.005 was considered statistically significant. Results: Peak incidence was seen in the 60-69 years age group (38.2%). Most frequent side of tumor was on the Left side (75%). Majority of the cases showed Moderate differentiated Adenocarcinoma (51.3%) and majority of the patients were belonging to T3 stage of the tumor 25 xxv (53%). TNM Stage II (28%) had more cases followed by TNM Stage II (28%). TILs was graded according to ITWG Methodology: The percentage of TILs was categorized into 3 groups: low (0-10%), intermediate (15-50%) and high (55-100%). Majority of the cases were of Low TILs (52.6%). Most of the cases for Tumor stroma ratio in colorectal cancer were of ≤50% (61.8%). 20.3% showed PDL1 expression and 44.8% showed MLH 1 expression. PDL1, MLH1 and TSR showed significant association with TILs. Significant association was noted between PDL1 and TILs with a p value of 0.012. MLH1 also showed significant association with TILs with a p value of 0.041. On comparing TILs and TSR the p value was 0.001 which was statistically significant. Conclusion: Study of 76 cases of Colorectal cancer showed PDL1 expression in 20.3% and MLH 1 expression in 44.8% cases. PDL1 and MLH1 showed a significant association on comparing with TILs in colorectal carcinoma. Also MLH1 showed significant association with TNM staging. Study of PDL1 and MLH1 helps in prognostification and management of Colorectal carcinoma.