Objective:Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. The identification of new simple, inexpensive and highly accurate markers for HCC diagnosis and screening is needed. This case-control study evaluates the role of annexin A2 and voltage-gated calcium channels α2δ1 subunit as serum biomarkers for HCC diagnosis.Methods:The study comprised three groups: group 1, 50 patients with an initial diagnosis of HCC associated with chronic hepatitis C virus infection; group 2, 25 patients diagnosed with chronic hepatitis C virus infection and cirrhosis without any evidence of HCC; and group 3, 15 healthy controls. All participants were subjected to clinical and laboratory investigations, and radiological scanning. The serum levels of alpha-fetoprotein (AFP), annexin A2, and the α2δ1 subunit were evaluated by using ELISA technique.Results:The serum levels of annexin A2 significantly increased in patients with HCC (10.4±2.5 ng/mL; P<0.001) or with cirrhosis (9.31±1.8 ng/mL;P<0.001) comparing to that of healthy controls (0.296±0.09 ng/mL). However, there was no significant difference in serum annexin A2 levels in patients with HCC comparing to those with cirrhosis. Serum α2δ1 subunit significantly increased in patients with HCC (20.12±3.7 ng/mL) comparing to that in patients with cirrhosis (10.41±3.4 ng/mL,P<0.001) and healthy controls (10.2±2.9 ng/mL,P<0.001). Conclusions:The serum α2δ1 subunit may function as a new biomarker for HCC diagnosis. Conversely, serum annexin A2 has low diagnostic value as an HCC marker, especially in patients with underlying cirrhosis.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. In an attempt to understand some potential mechanisms of persistence and oncogenicity of Hepatitis C virus (HCV)-related HCC, microfibrillar-associated protein 4 (MFAP4), fibrotic indices and oxidative status biomarkers were assessed in the sera of 50 patients with HCV-associated HCC, 25 patients with HCV-related liver cirrhosis and 15 healthy individuals. Serum oxidized Coenzyme Q10 (CoQ10) and malondialdehyde showed significant elevation in HCC patients compared to the control group (p < 0.001), as well as cirrhotic patients (p < 0.05 and p < 0.001, respectively), while serum glutathione content and superoxide dismutase activity were significantly decreased in HCC patients compared to the control group (p < 0.001). Serum MFAP4, aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on the 4 factors (FIB-4) and Forns index showed significant increase in HCC patients compared to the control group (p < 0.001), while only APRI and FIB-4 were significantly different between HCC and cirrhotic patients (p < 0.05), with a sensitivity of 86% and 92%, respectively, at cut off ≥0.7 for APRI and ≥1.57 for FIB-4. Therefore, increasing oxidative stress and fibrosis might mediate HCV induced cirrhosis and HCC. APRI and FIB-4 may be used as a simple non-expensive formula for the screening of HCC rather than MFAP4.

Objectives. Essential thrombocythemia (ET) is one of the myeloproliferative neoplasms characterized by a sustained elevation of platelet numbers with a tendency for thrombosis and hemorrhage. The aim of this work is to establish the relation between calreticulin, factor V Leiden, prothrombin G20210A, and MTHFR mutations in ET patients and the thrombotic risk of these patients. Methods. This study was carried out on 120 ET patients and 40 apparently healthy individuals as a control group. Results. There were increases in WBCs, PLT counts, PT, fibrinogen concentration factor V Leiden, and MTHFR mutation in ET patients as compared to the control group (P<0.05). Also, there were increases in WBCs, PLT counts, and hematocrit value in thrombosed ET patients as compared to the nonthrombosed ones (P<0.05). On the contrary, there was no significantly statistical difference in ET patients with JAK2 V617F positive mutation versus the JAK2 negative group (P>0.05) and in patients with cardiovascular risk factors versus patients with noncardiovascular risk factors (P>0.05). ET patients with factor V Leiden, prothrombin gene, and CALR mutations were more prone to thrombosis (odds ratio 5.6, 5.7 and 4.7, respectively). On the contrary, JAk2V 617F and MTHFR mutations have no effect on the thrombotic state of those patients. Conclusion. There is a significant increase risk of thrombosis in ET patients with CALR mutation, thrombophilic mutations, as well as factor V Leiden and prothrombin gene mutation with a risk of developing leukemic transformation.

What Is Known and Objective: Chronic myeloid leukaemia (CML) microenvironment is responsible for resistance of leukaemic cells to tyrosine kinase inhibitor, altered adhesion, increased proliferation and leukaemic cells growth and survival through the secretion of many soluble molecules. We aimed at monitoring soluble L-selectin (sCD62L) and secreted protein acidic and rich in cysteine (SPARC) levels in chronic phase chronic myeloid leukaemia (CP-CML) patients and assessing the impact of imatinib on these parameters.Methods: This prospective controlled clinical trial enrolled 35 subjects classified into two groups: control group included 10 healthy volunteers and CP-CML patients group included 25 newly diagnosed CP-CML patients received imatinib 400 mg once daily. sCD62L plasma levels, SPARC serum levels, breakpoint cluster region-Abelson1 (BCR-ABL1) %, complete blood count with differential, liver and kidney functions parameters were assessed at baseline and after 3 and 6 months of treatment.Results and Discussion: At baseline, sCD62L and SPARC were significantly elevated in CP-CML patients (p < 0.05) compared to control group. After 3 months of treatment, sCD62L was non-significantly decreased (p > 0.05), while surprisingly SPARC was significantly increased (p < 0.05) compared to baseline. Moreover, after 6 months of treatment, sCD62L was significantly decreased (p < 0.05) and SPARC was non-significantly decreased (p > 0.05) compared to baseline. In addition, sCD62L was significantly correlated with WBCs and neutrophils counts, while SPARC was significantly correlated with lymphocytes count at baseline and after 3 and 6 months of imatinib treatment. What Is New and Conclusion:The elevated levels of sCD62L and SPARC at diagnosis in CP-CML patients could reflect their roles in CML pathogenesis and the dynamic changes in their levels during imatinib therapy might suppose additional mechanisms of action of imatinib beside inhibition of BCR-ABL. Furthermore, imatinib showed a significant impact on sCD62L and SPARC levels during treatment period.

Background: Tumor-associated macrophages (TAM) are pivotal in remodeling of the tumor immune microenvironment and clinical outcome. Herein, we aim to evaluate the impact of immunohistochemical (IHC) expression of CD68 and CD163 in TAM on clinico-pathological features, patients' response to therapy and the overall survival (OS). Results: This retrospective study was performed on paraffin-embedded tissue blocks of 100 classic Hodgkin Lymphoma (cHL) cases diagnosed and treated at our Institution. Immunohistochemical scores of CD68 and CD163 were statistically related to bulky disease (p value = 0.005 for both), tumor stage (p value = 0.02 for both), International Prognostic Score (IPS) (p value = 0.04 and 0.02 respectively), and the overall response rate (ORR) (p value = 0.001). Additionally, CD163 was also statistically related to gender (p value = 0.02), serum albumin level (p value = 0.03), and B symptoms (p value = 0.04). HCV seropositivity did not relate to either CD68 or CD163 score. Using univariate analysis revealed that B symptoms, bulky disease, IPS ≥ 3, and CD163 > 25% were associated with lower OS (p values = 0.003, 0.006, 0.001, and < 0.001 respectively), while after multivariate cox regression analysis, B symptoms, IPS ≥ 3, and CD163 > 25% were related to inferior OS (p values 0.02, 0.02, and 0.003). Conclusion: CD163 expressing TAM is a powerful predictor for OS in cHL, unlike CD68.