Serum atrial natriuretic peptide: a suspected biomarker of breast cancer.

AIM OF THE STUDY: To assess serum levels of ANP in breast cancer female patients and its relationship to metastasis and some clinical parameters among those patients. MATERIAL AND METHODS: One hundred breast cancer patients with and without metastasis along with 20 healthy closely matched controls, were enrolled in the present cross sectional study. Background: To assess the serum levels of atrial natriuretic peptide in breast cancer Serum levels of ANP were assessed using ELISA. RESULTS: Mean serum levels of ANP breast cancer patients (13.9 ±10.1 ng/ml) were significantly elevated compared to healthy control group (2.2 ±1.3 ng/ml) (p < 0.001). The metastatic breast cancer patients showed significant elevated ANP levels (17.1 ±8.9 ng/ml) compared to non-metastatic group (6.4 ±8.8 ng/ml) p < 0.001. Within the metastatic group significant difference was detected between de novo metastatic, under follow-up, under hormonal control and locally advanced group (p = 0.007). CONCLUSIONS: This study showed significant elevated levels of ANP in the serum of metastatic breast cancer patients compared to non-metastatic patients. Within the metastatic group the lowest levels were detected in metastatic breast Cancer under hormonal treatment either tamoxifen or aromatase inhibitor.

High expression of GTPase regulator associated with the focal adhesion kinase (GRAF) is a favorable prognostic factor in acute myeloid leukemia.

BACKGROUND: GRAF is a recognized tumor suppressor gene that was found inactivated in AML. However, the prognostic role of a GRAF transcript has not been studied in patients with AML. METHODS: In this study, we investigated the expression of the GRAF transcript by real time quantitative PCR in 60 AML patients and 30 healthy age and sex matched controls. RESULTS: GRAF expression was significantly lower in patients with AML when compared to controls (P=0.008). There were no significant differences in clinical features, FAB subtypes and cytogenetic risk subgroups between patients with high and low GRAF expression levels. Kaplan-Meier analysis showed that patients with high GRAF expression had longer overall survival (OS). Multivariate analysis revealed that, besides WBC count, GRAF expression was also an independent prognostic factor for AML. CONCLUSION: We provide evidence that high GRAF expression is a favorable prognostic marker in patients with AML.

DNMT3A R882 mutations in patients with cytogenetically normal acute myeloid leukemia and myelodysplastic syndrome.

Several molecular markers have been described that help to classify patients with acute myeloid leukemia (AML), a heterogeneous hematopoietic tissue neoplasm, into risk groups. We determined the frequency of DNMT3A mutations, their associations with clinical and molecular characteristics and outcome, in primary, cytogenetically-normal AML (CN-AML) and CN-myelodysplastic syndrome (MDS). A total of 63 CN-AML and 16 CN-MDS patients were analyzed for mutations in DNMT3A, codon R822 by direct sequencing and mutation of NPM1 and FLT3/ITD. DNMT3A mutations were found in 17/63 (27%) of CN-AML and in 1/16 (6.3%) of CN-MDS patients. Patients with DNMT3A mutations were older (p=0.047), had higher white blood cell (WBC) counts (p=0.046), more often belonged to FAB groups M4 and M5 (p=0.017), and were more associated with NPM1 mutations (p=0.017), than those with wild-type DNMT3A. DNMT3A-mutated patients had shorter overall disease survival (p<0.001) and disease-free survival (p=0.014) when the entire patient cohort was considered, which remained significant in multivariate analysis. We conclude that DNMT3A R882 mutations are recurrent molecular aberrations in CN-AML, less frequent in CN-MDS, and that testing for R882 mutations may provide a useful tool for refining risk classification of CN-AML.

Metastatic Esophageal Carcinoma: Prognostic Factors and Survival.

BACKGROUND: Worldwide, esophageal cancer is the eighth most common cancer and the sixth leading cause of cancer-related death. At initial diagnosis, about 50% of esophageal cancer patients present with metastasis. The prognosis of metastatic esophageal cancer is poor with 5-year survival rate of less than 5%. METHODS: This is a retrospective study of stage IV esophageal cancer patients registered at Clinical Oncology and Nuclear Medicine department and Oncology Center Mansoura University in the period from 2009 to 2018 inclusive. Eligibility criteria were all pathologically proven stage IV esophageal cancer patients. The medical files of patients were reviewed. RESULTS: Most patients were ≥ 50 years (67.8%) with male predominance (76.7%). Middle third was the most common site of primary tumor (38.9%). Squamous cell carcinoma was more common with incidence of grade 3 (40%). T3-4 lesion was recorded in 61.1% and node positive in 66.7%. As regards metastasis; liver was the most common one (45.5%) followed by lung (30%). One-year survival rate was 25.6% with median survival time of 8 months. Multivariate analysis indicated that age (p = 0.03), site (p = 0.04), grade of primary tumor (p = 0.049), T classification (p = 0.0038), ECOG PS (p = 0.046), site (p = 0.026), and number of metastasis (p = 0.04) significantly affect prognosis while sex (p = 0.74) and histologic type (p = 0.94) do not. CONCLUSION: Metastatic esophageal carcinoma is a disease of poor prognosis especially in patients with the following criteria: old age, lower third location, high grade and large tumors, poor performance status, multiple sites of metastasis and presence of bone secondaries.

Prognostic significance of transforming growth factor ß receptor II in clinical stage III breast cancer patients - a pilot study.

BACKGROUND: Transforming growth factor-ß (TGFß) has a dual function in breast cancer, having a tumor suppressor activity in early carcinomas while enhancing tumor metastasis in advanced breast carcinoma. Consequently, the prognostic role of TGFß and its signaling cascade in breast cancer remain unclear. OBJECTIVE: To investigate the relationship between TßRII expression, clinic-pathological characteristics, and prognostic significance of TßRII expression in clinical stage III breast cancer. METHODS: Biopsy from the primary tumor was obtained from 30 newly diagnosed clinical stage III breast cancer patients before receiving any therapy. Expression of TßRII, ER, PR, Her2 and Ki-67 was assessed by immunohistochemistry. RESULTS: TßRII expression was positive in 66.7% of cases and was significantly associated with advanced nodal stage and distant metastases. After a median follow up of 42.3 months, TßRII was associated with poor disease-free survival and it was an independent factor for predicting the poor outcome for breast cancer patients, especially in node positive tumors, ER/PR positive and Her2-negative tumors. CONCLUSIONS: These findings suggest the usage of therapeutic drugs that target TGFß in advanced breast cancer patients may be effective. Nevertheless, blockage of the tumor promoting and sparing of the tumor suppressor effect of TGFß pathway should be taken into consideration. We suggest that these therapies might have more benefit in ER and PR positive tumors.

Evaluation of the Diagnostic and Prognostic Value of Syndecan-1 in Acute Leukemia Patients.

Syndecan-1 (also known as SDC-1 or CD138) is a transmembrane proteoglycan that is expressed in many hematological and solid tumors and affects the prognosis of those cancers. We conducted this study to investigate the prognostic role of syndecan-1 in acute leukemia. Forty cases of de novo acute leukemia patients, 24 with acute myeloid leukemia (AML) and 16 with acute lymphoblastic leukemia (ALL), presented at the Oncology Center of Mansoura University, Mansoura, Egypt, with a follow-up period of 26 months. Syndecan-1 was determined in serum and leukocytes by enzyme-linked immunosorbent assay (ELISA). The results from acute leukemia patients were compared with those of 15 healthy subjects. We observed that soluble syndecan-1 was higher in AML (median, 160.60 ng/ml) compared with ALL (median, 76.10 ng/ml) and healthy controls (median, 30.95 ng/ml). There was a significant correlation between syndecan-1 either in leukocytes or soluble form and response to treatment in patients with AML (p = 0.02 and p = 0.04, respectively), but these correlations were not statistically significant for ALL cases. Finally, there was a significant correlation between the soluble syndecan-1 level and overall survival in AML cases (p = 0.04), but the correlation was not significant for ALL cases. In conclusion, syndecan-1 is a useful biomarker for AML but not for ALL.

Clinicopathological study of occult hepatitis B virus infection in hepatitis C virus-associated hepatocellular carcinoma.

BACKGROUND: Occult hepatitis B virus infection (OBI) frequently occurs in patients with chronic hepatitis C (CHC) infection, but the influence of OBI on CHC outcome is still uncertain. The aim of the present study was to clarify the clinical and pathological characteristics of OBI in CHC-related hepatocellular carcinoma (HCC). PATIENTS AND METHODS: DNA was obtained from serum and tumor tissue of patients with hepatitis C virus (HCV)-related HCC with negative HBsAg and from patients with HCV-related liver cirrhosis. HBV-DNA was detected using qPCR. Clinicopathological features were compared between patients with HCC with and without OBI. RESULTS: On the basis of positive serum and tissue HBV-DNA typing, the overall frequency of OBI was 50% in patients with HCV-related HCC. HBV genotype D was the most dominant, constituting 35.3% of HCC cases. Almost 80% of patients with OBI had anti-HBc, whereas 20% of patients had no serological markers. Tissue HBV-DNA showed significant association with positive serum HBV-DNA, anti-HBc, and genotype D. There were no clinical differences between patients with HCC with and without OBI; however, patients with OBI tended to be younger. HCC cases with positive OBI were significantly associated with positive anti-HBc antibodies and late histological grades (3-4). Multivariate logistic regression analysis revealed that the presence of OBI was a predictor of more advanced HCC histological grades in patients with HCV infection. CONCLUSION: OBI was detected in 50% of HCV-infected patients with HCC. OBI was strongly associated with the presence of anti-HBc antibodies. Patients with HCC with positive OBI were younger and had more advanced HCC histological grades.

Influence of interleukin-15 polymorphism on the survival of adult patients with acute lymphoblastic leukemia in Egypt.

The aim of this study was to analyze the association of the rs10519612 and rs17007695 polymorphisms with the risk of acute lymphoblastic leukemia (ALL) and also to evaluate their impact on the survival of adult patients with ALL. The study included 164 adult patients with ALL and 158 healthy subjects as a control group who were genotyped for the interleukin-15 (IL-15) gene using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. We observed a higher risk of developing ALL for rs10519612 CC, rs17007695 TC and rs17007695 CC genotype carriers. There was increased risk for T-cell type in patients with the rs10519612 CC genotype. Notably, increased risk to develop B-cell type was found with rs17007695 TC and CC genotypes. There was no impact on overall survival or disease-free survival at 3 years. It is concluded that there is an association between both gene polymorphisms and the risk of ALL and with disease immunophenotype. However, there was no impact on the outcome of patients.

MTHFR A1298C and C677T gene polymorphisms and susceptibility to chronic myeloid leukemia in Egypt.

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating the intracellular folate metabolism which plays an important role in carcinogenesis through DNA methylation. We aimed to evaluate the association between MTHFR A1298C and C677T polymorphisms and the risks of chronic myeloid leukemia (CML). Eighty-five patients with CML and a control group containing 100 healthy, age and sex matched individuals were examined for MTHFR C677T and A1298C polymorphisms using polymerase chain reaction-restriction fragment-length (PCR-RFLP) method. The frequency of 677TT genotype in patients with CML was significantly higher compared to controls (OR=2.513, 95% CI: 0.722-4.086, P=0.025). No such association was shown for heterozygous 677CT (OR=1.010, 95% CI: 0.460-2.218, P=0.981). Moreover, for A1298C genotype, a statistically significant higher frequency of 1298CC was also detected in CML patients compared to control group (OR=1.1816, 95% CI: 0.952-3.573, P=0.036), 0.036). No such statistical significance was demonstrable for heterozygote 1298AC (OR=1.046, 95% CI: 0.740-1.759, P=0.092). In addition, patients with joint 677CT/1298AC or 677TT/1298CC genotypes showed an association with increased risk of CML (OR=1.849, 95% CI: 0.935-2.540, P=0.024; OR=1.915, 95% CI: 1.202-3.845, P=0.020 respectively). .A statistically significant increased risk of resistant to therapy was observed with 677CT and 1298AC genotypes (P=0.001, P=0.002 respectively). We conclude that both MTHFR 677TT and 1298CC polymorphisms have been associated with risk of CML and both 677CT and 1298AC genotypes are associated with higher risk of resistant to therapy.