TUMOR INFILTRATING LYMPHOCYTES PECULIARITIES IN DIFFERENT HISTOPATHOLOGICAL AND MOLECULAR SUBTYPES OF GASTRIC CARCINOMA.

Gastric carcinoma represents one of the major causes of cancer related mortality worldwide. Recently, immunotherapeutic means gave the new promise for the treatment of gastric carcinoma, although, not all patients benefit from this type of treatment. Tumor infiltrating lymphocytes (TILs) are considered as one of the promising prognostic and predictive biomarkers in solid tumors. However, the presence of TILs is not well characterised in different types of gastric cancer. The aim of our study was to characterise TILs profile in different histopathological and molecular subtypes of gastric carcinomas. We used standard haematoxylin and eosin staining (H&E) for evaluation of TILs and immunohistochemistry to detect molecular markers, including CDH1, Ki67, p53 and Her2. The results of our study revealed that TILs status varies significantly in different histological and molecular subtypes of gastric adenocarcinoma, which might be the reason for different prognosis in these patients. Also, high TILs status is significantly related to the presence of p53 mutations in both enteric type and diffuse type gastric carcinomas, which can be further explored for immunotherapeutic options in these patients.

THE STUDY OF THE EXPRESSION OF CDH1, KI67, P53 AND HER2 IN DIFFUSE GASTRIC CARCINOMA.

Gastric cancer represents the fifth most common malignancy and third most common cause of cancer deaths worldwide. There are two major types of gastric carcinoma: enteric type and diffuse type. Diffuse type gastric cancer is frequently associated with the mutations in E-cadherin coding gene CDH1. In cases of CDH1 mutations complete gastrectomy is indicated. CDH1 mutations are reflected with CDH1 protein loss by immunohistochemistry. The relationship between CDH1 mutations and other markers of tumour aggressiveness, such as tumour proliferation index and the presence of p53 mutations and Her2 amplification is not well studied. Therefore, the aim of our study was to analyse the correlation between CDH1 loss and the expression of Ki67 proliferation marker, mutant oncoprotein p53 and Her2. Standard immunohistochemistry was used to detect the following antigens: CDH1 (MCH-38, Invitrogen), Ki67 (EP5, Bio SB), p53 (DO-7, Leica) and Her2 (EP3, Bio SB). The study results showed that CDH1 mutations, reflected with CDH1 protein loss by immunohistochemistry are detected in 40% of diffuse gastric carcinomas, whilst it is not detected in enteric type gastric carcinomas. Diffuse gastric carcinomas with CDH1 mutations are characterised with more aggressive phenotype, particularly with the presence of higher Ki67 labelling index, p53 mutations and the presence of Her2 positivity. In cases of histological diagnosis of diffuse gastric carcinoma CDH1 testing is recommended.