Hepatocellular Carcinoma: Risk Factors, Diagnosis and Treatment

Hepatocellular carcinoma (HCC) is the most often primary cancer of the liver and is one if the leading cause of cancer-related death worldwide. The incidence of HCC has geographic distribution with the highest levels in countries with developing economies. Patients with hepatocellular carcinoma have poor prognosis despite the achievements in surgery techniques and other therapeutic procedures and it is a reason why continuous attention should be paid to this issue.This article provides an overview of this disease based on an extensive review of relevant literature. The article summarizes the current risk factors, diagnosis, staging and the management of HCC

TP53 Mutation in Correlation to Immunohistochemical Expression of P53 Protein in Patients with Hepatocellular Carcinoma

BACKGROUND: Mutations causing p53 inactivation are among the most common genetic alterations in human malignant tumours including hepatocellular carcinoma. Detection of p53 gene mutations in patients with hepatocellular carcinoma (HCC) should provide relevant data for the patients from the Republic of Macedonia and should allow the survivals additional therapeutic option as is gene therapy.AIM: We aimed to detect p53 gene mutations in HCC tissue, and to correlate them with the immunoexpression of p53 protein and multiple clinicopathologic characteristics of a tumour.MATERIAL AND METHODS: We analysed thirty patients with HCC for multiple clinic-pathological characteristics. Tumour tissue samples were immunostained for p53 and detection of p53 gene mutations was performed by polymerase chain reaction followed by Sanger sequencing.RESULTS: Changes in p53 gene sequence were detected in four patients (13.33%), one of them a polymorphism and the other three were missense point mutations with p53 immunoexpression of 50%, 0%, 0% and 90%, respectively. All patients with p53 mutations had cirrhosis. Two of them had Hepatitis B infection, moderately differentiated tumour and T2 status. There was one case with a well-differentiated tumour and one with T4 status. All of them were with vascular invasion. The size of the tumours was in the range of 2.5 cm to 16 cm. All 3 mutations were located in exon 7.CONCLUSION: Mutations in p53 gene are not always associated with obviously altered immunoexpression of p53 protein. Detection of p53 gene mutations is necessary in each case because the new therapeutic modalities offer to apply gene therapy

Tumour Lymphocytic Infiltration, Its Structure and Influence in Colorectal Cancer Progression

BACKGROUND: The role of the immune system in the control of tumour progression has been stressed, recently. Many studies indicate the fact that the immune system can prevent tumour progression in several types of human malignant neoplasms including colorectal cancer. According to some authors, a higher density of “tumour-associated lymphocytes†(TAL), in malignant neoplasms, correlate with prolonged survival of patients.AIM: This study aims to determine the structure and the influence of the immune cells, TAL, in the progression of colorectal cancer (CRC).PATIENTS AND METHODS: The study included 103 patients with CRC operated at the University Clinic of Digestive Surgery in Skopje, whose operative material was analysed at the Institute of Pathology, Medical Faculty in Skopje. The structure of tumor-associated cells and their density were determined and were correlated with neoplasm’s grade, local growth (T), positive lymph nodes, lymphatic invasion and stage of the disease.RESULTS: CD4+, CD8+ and CD20+ lymphocytes (Ly) were found in TAL. The density of TAL was significantly different in neoplasms with different T status, lymphatic invasion, patients with and without nodal metastasis and patients with a different stage of the disease. The density of CD4+, CD8+, and CD20+ cells were significantly different in neoplasms with different T. The density of CD8+ and CD20+ lymphocytes was lower in patients with nodal metastasis and higher stage.CONCLUSION: The density of tumor-associated lymphocytes can anticipate the disease progression in patients with colorectal cancer, and the density of TAL influences the control of tumour progression

HER2 Positive Gastric Carcinomas and Their Clinico-Pathological Characteristics

BACKGROUND: HER2 protein expression in gastric carcinoma, in correlation with existing, acknowledged prognostic factors which include the parameters that determine the TNM stage of the disease, could become the basis for ongoing research in the field of molecular targeted and personalised therapy.AIM: To determine the expression of the HER2 protein in gastric carcinoma and to correlate the expression of a HER2 protein with clinicopathological characteristics of the disease.MATERIAL AND METHODS: The data of HER2 protein expression and the parameters of the TNM classification were obtained from the histopathological reports of the Institute of Pathology in Skopje, and for the clinical stage we used patient’s files from the University Clinic for Abdominal Surgery in Skopje.RESULTS: The analysis of the correlation of HER2 protein expression and TNM classification parameters pointed out a significant correlation between HER2 protein expression and intragastric localisation of gastric carcinoma (P = 0.005), and the tumour grade of differentiation (P = 0.034). There was also a positive correlation between HER2 protein expression pattern and positive lymph nodes in patients with gastric carcinoma (P = 0.03). The expression pattern of HER2 +++ was significantly more common registered in patients with positive lymph nodes (P = 0.03)CONCLUSION: The expression of HER2 protein could represent a biological marker with prognostic and predictive value in patients with gastric carcinoma. Considering the high mortality rate in patients with gastric carcinoma and lack of international standardised therapeutic approach, research of the role and significance of HER2 overexpression and Trastuzumab therapy may prove useful in the development of new therapeutic strategies

Tertiary Lymphoid Structures in Colorectal Cancers and Their Prognostic Value

Abstract Introduction: Tumor-infiltrating lymphocytes (TIL) in tumor stroma are considered to be involved in elimination of malignant cells and in prevention of metastasis formation. TIL are consisted of T lymphocytes including cytotoxic lymphocytes that are a constituent part of the effector mechanism of anti-tumor immunity and B lymphocytes that can form tertiary lymphoid structures (TLS). TLS have been described in several solid tumors and in colorectal carcinoma (CRC) and they influence on the local and systemic anti-cancer response. The aim of this study was to quantify the presence of TLS in CRC patients and to determine their role in tumor progression. Patients and methods: The study included 103 patients with CRC who underwent surgery at the University Clinic of Digestive Surgery in Skopje, whose operative material was analyzed at the Institute of Pathology, Medical Faculty in Skopje. The density of TLS was determined and correlated with neoplasm status of local growth (T), positive lymph nodes, lymphatic invasion, stage of the disease and tumor grade. Results: The density of TLS was significantly higher in patients with higher stage, lower T status, negative lymph nodes, in patients with no lymphatic invasion and with better differentiated tumors. Conclusion: The density of TLS plays an important role in controlling the tumor growth and it can be a parameter for neoplasm progression in CRC patients. The density of TLS has influence on the control of tumor progression

Hepatocellular Carcinoma: Risk Factors, Diagnosis and Treatment

Citation: Janevska D, Chaloska-Ivanova V, Janevski V. Abstract Hepatocellular carcinoma (HCC) is the most often primary cancer of the liver and is one if the leading cause of cancer-related death worldwide. The incidence of HCC has geographic distribution with the highest levels in countries with developing economies. Patients with hepatocellular carcinoma have poor prognosis despite the achievements in surgery techniques and other therapeutic procedures and it is a reason why continuous attention should be paid to this issue. This article provides an overview of this disease based on an extensive review of relevant literature. The article summarizes the current risk factors, diagnosis, staging and the management of HCC