Expression of Alpha-Methyl Acyl-Co-enzyme Racemase in Gastric Carcinomas

Abstract

Introduction: Alpha-Methyl Acyl-Co-enzyme Racemase (AMACR, EC 5.1.99.4, also known as P504S) is a mitochondrial and peroxisomal enzyme involved in branched fatty acids oxidation. High dietary intake of branched fatty acids may result in overproduction of AMACR, which is associated with the development of many cancers including prostate, kidney, breast, ovary, liver and gastrointestinal cancers. Several reports have also shown an association between consumption of fat and increased risk of gastric cancer, especially intestinal type gastric carcinomas. Aim: To determine and compare the expression of AMACR in clinical types and various histological grades of gastric carcinomas. Materials and Methods: This was a cross-sectional study conducted from November 2016 to May 2018 at Osmania Medical College/General Hospital, Hyderabad, Telangana, India. The tissue cores of the included biopsied samples of 50 gastric carcinomas, with regions of interest were removed to prepare a tissue microarray and Immunohistochemical (IHC) staining for AMACR was performed. The stained slides were graded based on the intensity of staining and results were evaluated using Chi-square test. Results: Of the 50 gastric carcinomas (32 males and 18 females; age range: 22-80 years) cases studied, 26 were intestinal type and 24 were diffuse type. According to cancer grade, 17 were well differentiated, nine were moderately differentiated and 24 were poorly differentiated. Abnormal AMACR staining was seen in 73.07% (19) cases of well and moderately differentiated adenocarcinoma and 33.33% (8) cases of poorly differentiated adenocarcinoma. The AMACR staining was found to be statistically significantly associated with the differentiation grading of the tumour (p-value 0.016). Abnormal staining for AMACR was seen more in well differentiated compared to moderately and poorly differentiated carcinomas. IHC expression of AMACR showed a statistically significant correlation with Lauren’s type of gastric cancer (p-value 0.005). Conclusion: The AMACR is a racemase present in the cytoplasm; cytoplasmic staining is observed in gastric carcinoma and also with histological grade. Abnormal staining for AMACR was seen more in well differentiated compared to moderately and poorly differentiated carcinomas. The expression of AMACR was significantly higher in intestinal type gastric carcinoma. Hence, the role of AMACR as a target for treating gastric cancer seems to be promising. Further studies are required to establish the role of AMACR as a diagnostic, therapeutic and prognostic tool in gastric malignancies

Keywords

• diffuse type
• gastric cancer
• intestinal type