Aberrant ecotropic viral integration site-1 (EVI-1) and myocyte enhancer factor 2 C gene (MEF2C) in adult acute myeloid leukemia are associated with adverse t (9:22) & 11q23 rearrangements.

Acute myeloid leukemia (AML) shows multiple chromosomal translocations & point mutations which can be used to refine risk-adapted therapy in AML patients. Ecotropic viral integration site-1 (EVI-1) & myocyte enhancer factor 2 C gene (MEF2C) are key regulatory transcription factors in hematopoiesis and leukemogenesis & both drive immune escape. This prospective study involved 80 adult de novo AML patients recruited from Oncology Center, Mansoura University, between March 2019 and July 2021. The MEF2C and EVI1 expression were measured using a Taqman probe-based qPCR assay. The results revealed that EVI1 and MEF2C expression were significantly elevated in AML patients as compared to control subjects (p = 0.001. 0.007 respectively). Aberrant expressions of EVI1 and MEF2C showed a significant negative correlation with hemoglobin levels (p = 0.034, 0.025 respectively), & bone marrow blasts (p = 0.007, 0.002 respectively). 11q23 translocation was significantly associated with EVI1 and MEF2C (p = 0.004 and 0.02 respectively). Also, t (9;22) was significantly associated with EVI1 and MEF2C (p = 0.01 and 0.03 respectively), higher expression of EVI1 and MEF2C were significantly associated with inferior outcome after induction therapy (p = 0.001 and 0.018 respectively) and shorter overall survival (p = 0.001, 0.014 respectively). In conclusion, EVI1 & MEF2C were significantly expressed in AML cases. EVI1 & MEF2C overexpression were significantly associated with 11q23 rearrangements and t (9;22) and were indicators for poor outcome in adult AML patients; These results could be a step towards personalized therapy in those patients.

High FOXA1 immunohistochemical expression level associates with mucinous histology, favorable clinico-pathological prognostic parameters and survival advantage in epithelial ovarian cancer.

BACKGROUND: Forkhead box (FOX) A1 is a potential therapeutic biomarker that has been investigated in various human cancers. Limited data exist about FOXA1 biologic role in epithelial ovarian cancer (EOC). AIM: This study assessed FOXA1 immunohistochemical (IHC) expression and evaluated its association with clinico-pathological parameters in EOC including overall and disease-free survivals (OS, DFS) and patient's outcome. METHODS: Patient's socio-epidemiologic, clinical, radiological, laboratory, surgical, and follow-up data were collected. After histopathologic typing, grading and staging, FOXA1 IHC expression was scored in 98 EOC specimens. Clinico-pathological associations were investigated in high-and low-FOXA1 expression groups using appropriate statistical methods. Kaplan-Meier method was used for survival analysis. RESULTS: FOXA1 tumor cell nuclear staining was detected in 63.3% of EOC with weak, moderate and strong scores (28.6%, 12.2% and 22.5% respectively). Comparing high- and low-expression groups (34.7% and 65.3% respectively), high FOXA1 was associated with larger tumors, low mean serum CA-125, tumor histopathology (mucinous and low-grade serous), type I EOC, limited tumor's anatomical extent, absence of nodal or distant metastases and omental nodules, earlier FIGO stages, non-recurrent tumors and survival advantage with longer and OS and DFS (all p ≤ 0.05). Independent predictors of high FOXA1 expression included: omental nodules, tumor's anatomical extent and tumor's size (p ≤ 0.001, = 0.046 and = 0.023 respectively). CONCLUSION: FOXA1 is frequently expressed in EOC notably mucinous and low-grade serous carcinomas in association with favorable prognostic clinico-pathological parameters and longer OS and DFS. It likely has a suppressor function in EOC and could be recommended as a prognostic and therapeutic biomarker.

Study of single nucleotide polymorphism of vascular endothelium factor in patients with differentiated thyroid cancer.

BACKGROUND: Genetic alterations and high levels of the vascular endothelial growth factor (VEGF) are presumptive risk factors for differentiated thyroid cancer (DTC). OBJECTIVE: This work aims to study the presence of - 634G/C polymorphism of vascular endothelial growth factor (rs2010963) and its' serum level in patients with DTC and comparing these results with those of the control subjects. MATERIAL AND METHOD: The study was a retrograde case-control study that included seventy patients with DTCin addition to seventy apparently healthy control subjects. Blood sample was taken and subjected to study of - 634G/C VEGF polymorphism (rs2010963) by real time PCR and measurement of its' plasma level by immunoassay kit (ELISA). RESULTS: Regarding genotyping of VEGFA - 634G/C (rs2010963) polymorphism, there was significant increase in CG and GG genotypes (28.6%, 18.6% respectively) among patients compared to control subjects (20.0%, 4.3% respectively) and significant increase in CC genotype in control subjects (75.7%) compared to patients (52.9%), P = 0.001. The VEGF mean ± SD level was significantly elevated in patients compared to control subjects (1215.81 ± 225.78 versus 307.16 ± 91.81, P = 0.006). Moreover, there was significant increase in VEGF levels in patients with CG and GG genotypes (1295.9 ± 68.74, 1533.08 ± 109.95, respectively) compared to patients with CC genotype (1061 163.25), P = 0.001). CONCLUSION: There was significant increase in GG and CG genotypes in patients with DTC compared to control subjects which may suggest a predisposing role for these genotypes in development of DTC. Moreover, there was significant increase in serum level of vascular endothelial growth factor in patients with GG and CG genotypes which may reflect the mechanism of these genotypes in development of DTC.

Isolated Myeloperoxidase Immunohistochemical Expression in Bone Marrow Biopsy Depicts Clinical Outcomes in Adults with Typical B-Acute Lymphoblastic Leukemia.

INTRODUCTION: Recently, isolated myeloperoxidase expression (isoMPO) has been documented in B-acute lymphoblastic leukemia (B-ALL) and several contradictory studies addressed its clinical significance in pediatric patients. AIM: In this study, isoMPO was evaluated in bone marrow biopsies (BMB) from adults with B-ALL using immunohistochemistry (IHC) in relation to a number of risk-stratification factors and patients' outcomes. METHODS: Sixty B-ALL adult patients were selected upon electronic database search. Demographic, clinical, laboratory, therapy and survival data were reviewed and tabulated. Flowcytometry (FCM), histopathology and IHC available material were reviewed to confirm the diagnostic criteria according to our standard laboratory protocols. IHC was performed on BMB using antiMPO. Cases were divided into MPO+ve and MPO-ve based on a 3% blast cell staining threshold. RESULTS: Using IHC, 26.7% of B-ALLs were MPO+ve, in most of which ≥10% of blasts were stained. Among standard risk-stratification factors, isoMPO was associated with a mean WBC count above 30x109/L. MPO+ patients achieved therapeutic complete remission at lower rates and were more prone to progressive/refractory disease and relapse. There was a concordant expression of MPO in FCM and IHC. All of the aforementioned parameters reached the level of significance when compared to the MOP-ve group. Kaplan-Meier curves revealed a significantly lower survival probability for the MPO+ group than the MOP-ve one (p= 0.0066; Log-rank test) and also when separating MPO+ and -ve patients by gender (p= 0.0033; Log-rank test). CONCLUSION: isoMPO occur in a considerable percentage of B-ALL in adults contributing to misdiagnosis. It depicts poor outcomes and might be introduced as a B-ALL risk-stratification factor.
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