Clinical Significance of MAP-7 and FOXC1 in Egyptian Acute Myeloid Leukemia Patients.

PURPOSE: The present study aimed to report the clinical correlations and prognostic significance of microtubule-associated protein-1 (MAP-7) and forkhead box transcription factor-C1 (FOXC1) expression in Egyptian patients with newly diagnosed acute myeloid leukemia (AML). METHODS: The study included 80 adults with newly diagnosed AML. Laboratory investigations included complete blood count, morphological examination of bone marrow aspirate, immunophenotyping, conventional karyotyping and molecular study for fms-like tyrosine kinase 3 (FLT3), nucleophosmin-1 (NPM1) and CCAAT/enhancer binding protein α (CEBPA) mutations. MAP-7 and FOXC1 expressions in bone marrow were determined using RT-PCR. Patients were followed for a median (range) period of 6.4 (1.0-35) months. The study outcomes included treatment response, progression-free survival (PFS) and overall survival (OS). RESULTS: Patients with low FOXC1 expression had significantly lower mortality rate (60.0 % versus 84.6 %, p=0.021), significantly longer PFS duration and significantly longer OS. No significant differences were noted between MAP7 expression groups regarding treatment response, mortality rate, PFS duration and OS duration. Interestingly, a significant direct correlation was noted between FOXC1 and MAP7 expressions (r=0.25, p=0.027). CONCLUSIONS: FOXC1 and MAP7 expressions are significantly correlated. High expression of FOXC1 in Egyptian population may be related to shorter OS and PFS.

Post-Treatment Change in mir92a Levels Predicts AML Prognosis Better than Single Baseline or Post-Treatment Values.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous malignant disorder. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. METHODS: The study included 44 adult AML patients diagnosed according the WHO classification criteria. Circulating levels of mir92a were measured at baseline and on the 28th day after induction of treatment. Levels were classified as high (≥ median) or low (< median) expression. Change of mir92a levels was calculated by subtracting the baseline result from the post-treatment result. The study outcomes included achievement of complete remission (CR) at 28 days post-induction, progression free survival (PFS), and overall survival (OS). RESULTS: Patients with increased mir92a levels had significantly higher CR rate. They also had significantly lower mortality rate (3.7% versus 88.2%, p < 0.001), longer PFS time, and longer OS time. Cox-hazard regression analysis identified female gender and increased mir92a levels as independent predictors of PFS while only increased mir92a levels were identified as independent predictor of OS. CONCLUSIONS: Post-treatment change in levels of circulating mir92a can provide better prediction of PFS and OS in AML patients.

Treatment outcome of doxorubicin versus idarubicin in adult acute myeloid leukemia.

PURPOSE: The present study aimed to compare treatment outcome of idarubicin versus doxorubicin in combination with Ara-C as induction therapy for untreated AML patients. PATIENTS AND METHODS: This retrospective study included 143 patients with de novo AML. All patients received full dose of standard induction therapy (3 + 7) using anthracyclines (doxorubicin or idarubicin) and cytarabine. RESULTS: The studied groups had comparable CR. No significant differences were noted between the studied groups regarding DFS and OS. The DXR group had significantly lower cost in comparison to IDA group. CONCLUSIONS: Idarubicin doesn't have a clear advantage over doxorubicin in treatment of AML.

Prognostic Values of MicroRNA-21 and Ki-67 in Diffuse Large B-Cell Lymphoma Patients: Egyptian Experience.

BACKGROUND: MicroRNA-21 (miR-21) is a small non-coding RNA which influences tumorigenesis by inhibiting the expression of target genes. Ki-67 is a nucleolar antigen highly correlated with the rate of proliferating cells. In this study, we aimed to evaluate the prognostic impact of miR-21 and Ki-67 in DLBCL disease in a cohort of Egyptian patients. METHODS: We prospectively enrolled 53 newly diagnosed DLBCL patients. RT-PCR was used to evaluate the plasma expression levels of miR-21. Tissue Ki-67 was assessed using immunohistochemistry (IHC) of lymph node biopsy sections. Overall survival (OS) and progression free survival (PFS) were the primary outcomes. RESULTS: miR-21 expression was significantly higher in patients with DLBCL in comparison to controls (p < 0.001). The median Ki-67 expression was 70% and positivity ranged from 25% to 100%. Response to treatment was achieved in 23 patients (43.4%). Higher miR-21 was associated with poor response to treatment (p = 0.03). Although patients' age was a significant predictor of OS in univariate analysis, none of the studied factors could predict OS in multivariate analysis. However, we found that Ki-67 expression was a significant predictor of PFS in both univariate and multivariate analyses. CONCLUSIONS: The study suggested that plasma miR-21 might be a valuable non-invasive prognostic marker of response to treatment in DLBCL patients. Moreover, Ki-67 is a potential significant predictor of both OS and PFS in those patients.

Prognostic Value of Tumor Associated Macrophage Markers CD163 and CD68 Immunohistochemistry in Classical Hodgkin Lymphoma.

BACKGROUND: Tumor associated macrophages have been implicated in the pathogenesis of classical Hodgkin's lymphoma and have been suggested to have a negative impact on outcome. The aim of this study is to determine the expression and the prognostic impact of CD163 and CD68 markers of the tumor associated macrophages, in the initial positively infiltrated bone marrow biopsy specimens of our subjects by immunohistochemistry and to corre¬late their expression with other clinical and laboratory prognostic factors. METHODS: This study was conducted on fifty-one patients with de novo classical Hodgkin's lymphoma, presenting to the Clinical Pathology Department at the National Cancer Institute, Cairo University. CD163 and CD68 were detected in the initial bone marrow biopsy specimens from our subjects by immunohistochemistry. RESULTS: The present study included 51 patients with CHL. They comprised 24 males (47.1%) and 27 females (52.9%) with an age of 32.9 ± 14.5 years. After treatment, 33 patients (64.7%) achieved complete remission while 18 patients (35.3%) failed. Comparison between patients with CR and patients without revealed significantly lower CD68 expression [median (IQR): 30.0 (15.0 - 47.5%) versus 55.0 (43.8 - 55.0%), p = 0.003] and CD163 expression [25.0 (10.0 - 37.5%) versus 45.0 (0.35 - 55.0%)] in CR patients. Binary logistic regression analysis identified CD68 and CD163 expressions as significant predictors of CR in univariate and multivariate analyses. CONCLUSIONS: The expressions of both tumor-associated markers, CD68 and CD163, are significant predictors of CR in patients with CHL.

MicroRNA-92a as a marker of treatment response and survival in adult acute myeloid leukemia patients.

This prospective study assessed circulating miR-92a levels in acute myeloid leukemia (AML) at diagnosis and after induction therapy and followed patients for a maximum of 30 months. The study included 63 consecutive adult AML patients. Circulating miR-92a levels were assessed using real-time polymerase chain reaction (RT-PCR). There was significant rise of miR-92a expression after induction (median (range): 0.297 (0.001-3.438)) in comparison to the reported levels at diagnosis (median (range): 0.236 (0.001-3.305)). Post-induction levels of miR-92a are significantly higher in patients who achieved CR in comparison to patients without CR (median (range): 0.408 (0.017-3.438) vs. 0.01 (0.001-1.010), p<.001). Cox hazard regression analysis identified miR-92a as a significant predictor of OS and DFS in univariate and multivariate analyses. In conclusion, baseline circulating miR-92a in AML patients may be a useful prognostic marker of treatment response and survival over 2.5 years follow up.

Prognostic and Therapeutic Value of Day 14 Bone Marrow Aspiration in Adult Acute Myeloid Leukemia Patients.

BACKGROUND: Early blast clearance to induction chemotherapy in acute myeloid leukemia (AML) is an important prognostic indicator of treatment outcome in addition to genetics and molecular genetics. We evaluated the prognostic value of bone marrow aspiration (BMA) at day 14 (D14) and impact on outcome to asses the timing of a second induction. PATIENTS AND METHODS: This retrospective study included 303 adult AML patients managed at the National Cancer Institute, Cairo University, from the beginning of 2010 to the end of 2014. RESULTS: Median age was 34 years (range, 18-67 years). Sixty-six percent had early blast clearance with < 5% blasts and 34% had ≥ 5% blasts at BMA D14; 38 patients died early during or shortly after induction. Initial blast load (bone marrow and peripheral blood) and initial platelet count were significantly higher in those with disease that did not respond to therapy compared to those whose disease did respond to therapy at D14 (P < .001, .035, and .006, respectively). The median disease-free survival for early blast clearance at D14 was 18.5 months, versus 18.7 months for those with late response to therapy (day 28), and was only 1.3 months for patients who received immediate second-line therapy on the basis of BMA D14 (P < .001). The median overall survival for early blast clearance was 13.6 months, versus 7.2 months for those with late response to therapy, and only 1.3 months for patients who received immediate second-line therapy on the basis of BMA D14 (P < .001). CONCLUSION: BMA D14 has a significant prognostic impact on the therapeutic outcome of AML patients (complete remission, disease-free survival, and overall survival); however, a second induction in patients with BMA D14 blasts > 5% should be delayed until neutrophil recovery to minimize death in aplasia.

ssociation of Cytochrome P450-1B1 Gene Polymorphisms with Risk of Breast Cancer: an Egyptian Study.

It is thought that population characteristics of breast cancer may be due to a variation in the frequency of different alleles of genes such as CYP1B1. We aimed to determine the association of CYP1B1 polymorphisms in 200 breast cancer cases and 40 controls by PCR-RFLP. Frequencies were assessed with clinical and risk factors in Egyptian patients. The genotype LV and the Leu allele frequencies for patients and controls were 42.9% and 50%, and 52.9% and 53.3%, respectively), with no significant differences observed (P values = 0.8 and 0.6, respectively). There was also no significant association between genotypes and any risk factors for cases (>0.05) except laterality and metastasis of the tumor (P values=0.006 and 0.06, respectively). The CYP1B1 polymorphism Val432Leu was not associated with breast cancer in Egypt, but may provide clues for future studies into early detection of the disease.

Association of Viral Infections with Risk of Human Lymphomas, Egypt.

BACKGROUND: The aim of this study was to determine and evaluate the association of different viral infections, with hepatitis B and C viruses, Epstein-Barr virus, cytomegalovirus and human herpes virus-8 (HBV, HCV, EBV, CMV, HHV-8) with the risk of lymphomas (Hodgkin and non-Hodgkin) among Egyptian patients, and correlate with the histopathological staging and typing as well as the prevalence of combined infections. MATERIALS AND METHODS: A total of 100 newly diagnosed lymphoma patients with 100 healthy age and sex matched normal controls were assayed for viral infection using enzyme linked immunosorbant assay (ELISA) followed by real time polymerase chain reaction (RT-PCR). RESULTS: Our results showed a high statistical significant difference between cases and controls as regards clinical and laboratory findings (<0.001 and=0.003). A high statistical difference was seen for the association of most viruses and lymphoma cases (<0.001) except for positive HBs Ag, positive CMV IgG and HHV-8 (p=0.37, 0.70 and 1.0 respectively). No statistical significant difference was found between Hodgkin (HL) and non-Hodgkin (NHL) as regards viral prevalence except HCV antigen, 57.1% for HL and 26.5% for NHL (p = 0.03). Only, HBV DNA showed a high significant value among infiltrated bone marrow cases (p=0.003) and finally, a high significant association of 2 combined viral infections with infiltrated bone marrow lymphoma cases (p=0.04). CONCLUSIONS: Our results showed that infection with HBV, HCV, CMV and EBV were associated with increased risk of lymphoma among the Egyptian population. Detection of new associations between infectious agents and risk of cancer development will facilitate progress in elaboration of prophylactic measures, early diagnostic methods and, hopefully, novel therapy of malignant tumours.

Relation of BAALC and ERG Gene Expression with Overall Survival in Acute Myeloid Leukemia Cases.

BACKGROUND: The objectives of this study were to evaluate the expression of brain and acute leukemia, cytoplasmic (BAALC) gene and erythroblast transformation-specific related gene (ERG) in de novo cases of acute myeloid leukemia (AML) and identify roles in disease progression and outcome. MATERIALS AND METHODS: This study included 50 newly diagnosed AML patients, along with 10 apparently healthy normal controls. BAALC and ERG expression was detected in the bone marrow of both patients and controls using real-time RT-PCR. RESULTS: BAALC and ERG expression was detected in 52% of cases but not in any controls. There was a statistically significant correlation between BAALC and ERG gene expression and age (p- value=0.004 and 0.019, respectively). No statistical significance was noted for sex, lymphadenopathy, hepatomegaly, splenomegaly, other hematological findings, immunophenotyping and FAB sub-classification except for ERG gene and FAB (p-value=0.058). A statistical significant correlation was found between response to treatment with ERG expression (p-value=0.028) and age (p-value=0.014). A statistically significant variation in overall survival was evident with patient age, BM blast cells, FAB subgroups, BAALC and ERG expression (p-value= <0.001, 0.045, 0.041, <0.008 and 0.025 respectively). CONCLUSIONS: Our results suggest that BAALC and ERG genes are specific significant molecular markers in AML disease progression, response to treatment and survival.

Prevalence of bone marrow necrosis in Egyptian cancer patients referring to the National Cancer Institute.

BACKGROUND: Bone marrow necrosis is a relatively rare entity which has been associated with a poor prognosis. It is most commonly found in patients with neoplastic disorders and severe infections. METHODS: The study comprised examination of 5043 bone marrow biopsy specimens performed at the National Cancer Institute, Cairo University, over 7 years period (March 2004-March 2011). It included 5 years retrospective (2867 archived samples) and 2 years prospective (2176 samples). RESULTS: Bone marrow necrosis was diagnosed in fifteen out of 5043 examined specimens with a percentage of 0.3% and ranged from mild to massive according to semiquantitative estimation. Prognosis of all patients was poor with survival not exceeding 6 months from the date of marrow necrosis diagnosis. CONCLUSION: In Egyptian patients, bone marrow necrosis in association with malignancy is a rare disorder which is accompanied by a poor outcome.