Objective: Triple negative breast cancer is an aggressive variant of breast cancer; it forms about 15% of breast cancer cases. It lacks the responsiveness to hormonal and targeted therapies. Anthracyclines remain the treatment option for these patients. Anthracyclines are cardiotoxic, so predicting sensitivity of response by biological predictors may have a role in selecting suitable candidates for these drugs. Material and methods: This study included 50 TNBC cases, from National Cancer Institute, Cairo University(NCI-CU), Egypt, who underwent surgery and received adjuvant chemotherapy. Archived blocks were obtained and immunostaining for Ki-67 LI and Fluorescent In situ Hybridization (FISH) technique to assess TOP2A gene copy number and chromosome 17CEP status were done. Analysis of association between TOP2A alterations and CEP17 polysomy as well as Ki-67 LI with other clinicopathological parameters was done. Associations between the biological markers and event free survival (EFS) and overall survival (OS), were also performed. Results: TOP2A alteration was seen in 9/50 cases (5 amplified and 4 deleted). CEP17 Polysomy was detected in 14% of cases. Most of patients (80%) showed Ki-67 LI ≥20%. There was a significant association between TOP2A gene and CEP17 status. Outcome was better with abnormal TOP2A gene status and CEP17 polysomy, radiotherapy and combined anthracyclines and taxanes in the adjuvant setting, however P-values were not significant. Conclusion: TOP2A gene alterations and CEP17 polysomy may have prognostic and predictive role in TNBC treated with adjuvant Anthracyclines.

HER-2 and TOP2A genes amplification are 2 separate genetic yet closely related events in breast cancer. Polysomy of chromosome 17 is proposed to be an early event in occurrence of TOP2A gene amplification. Further studies regarding effect of TOP2A gene in response to anthracyclines in Egyptian population should be planned for to establish its role in therapeutic planning.

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Immune thrombocytopenia (ITP) is a multifactorial disease in which both environmental and genetic factors have been implicated. The study aimed to investigate a possible association of single nucleotide polymorphisms (SNPs rs266085 and rs2839693) in the stromal derived factor-1 (SDF-1) gene and its association to ITP and effect on ITP severity and response to treatment. Genomic DNA was extracted from peripheral blood and polymorphism in SDF-1 gene rs266085 and rs2839693 was analyzed using PCR-restriction fragment length polymorphism technique in DNA extracted from 60 children with ITP together with 90 healthy controls. On analysis of SDF-1 rs266085 polymorphism, there was a high frequency of CC genotype in cases than controls and that difference was significant at codominant, overdominant, and dominant models (P<0.05). Furthermore, carriers of the CC genotype were more susceptible to severe ITP at onset, steroid dependency, and chronicity than carriers of other genotypes (P<0.05). Otherwise, no significant differences between ITP patients and controls as regard SDF-1 rs2839693 genotypes and alleles, and we did not find a relation between this polymorphism and ITP severity, steroid dependency, or duration. SDF-1 gene rs266085 SNP C allele is associated with susceptibility to develop ITP as well as increases the risk for severe ITP at onset, chronic ITP and steroid dependency.

Ki-67 is a reliable and reproducible marker for grading of NETs and more superior than mitotic rate.

Background and aim Axillary lymph node metastasis is the most important prognostic factors in breast carcinoma. The metastatic burden can be determined either by the number of lymph nodes with metastases (pN) or by the metastatic ratio (LNR), which is the ratio of positive nodes to the total nodes removed. The aim of the present investigation was to quantify the anatomic distribution of axillary lymph nodes by levels as well as to compare the metastatic burden of breast cancer at different nodal levels. A hypothetical model of incomplete lymphadenectomy was tested to determine the risk of such operations if performed in Egyptian patients. Patients and methods This study included 110 patients.In all operations, axillary dissection was complete including the three levels of nodes. The total series (110 patients) was used to study the anatomic distribution of axillary nodes at different levels as well as to study the rate of metastases at different levels. However, cases with positive nodes (56 patients) were used to determine the metastatic burden. ResultsThe total number of lymph nodes removed in the 110 cases was 2463 nodes. There were 1196 (48.6%) nodes at level I, 919 (37.3%) at level II, and 348 (14.1%) at level III (P < 0.001). The rate of lymph node metastases was 50.9%. The rates of node metastases at axillary levels I, II, and III were 50.9, 34.5, and 20%, respectively. The median number of metastatic lymph nodes in node-positive cases was 4, whereas the median numbers per level were 3, 4, and 3, respectively. The median lymph node ratio (LNR) for positive patients was 0.18, whereas the median LNRs per level were 0.3, 0.5, and 1, respectively (P < 0.001). Most of the node-positive patients (55.4%), according to LNR, were considered to be at low risk (r 0.2), whereas 28.6% were at an intermediate risk (0.2-0.65) and 16% were at a high risk (> 0.65%).Conclusion It can be concluded from this study that Egyptian patients with operable breast cancer present at a late stage (63.6% of tumors are >T1 and 50.9% have positive nodes). Anatomically, axillary nodes are commonly located (85.9%) at levels I and II and most metastases (86.8%) affect these two levels. However, level III is also involved in metastases in 20% of patients, hence the importance of a complete axillary lymphadenectomy in Egyptian patients.

Being the most common cause of female deaths worldwide, breast cancer (BC) is intensively studied over the last two decades. In the present investigation, we evaluated the promoter methylation of three cancer-related genes; PARP-1, p21, and Rb in 10 bi-matched BC samples (ductal carcinoma and lobular carcinoma) included the core tumor and the adjacent normal tissue. H&E-stained histopathological sectioning revealed grade 2 and grade 3 tumor cells. Methylation-specific PCR (MSP) was performed using methylated (M) and unmethylated (U) primers for the three genes understudy. Histone acetyltransferase was measured in tumor and healthy tissues. A variation in the methylation state of the promoter region of the three genes were observed in core tumor and healthy tissue. PARP and Rb were hypermethylated in tumor tissues while p21 was partially methylated. HAT activities were positively correlated with the methylation pattern observed in healthy tissues, as HAT was highly expressed in healthy vs. tumor tissues. The obtained data might indicate that patients might be at risk of BC recurrence after being subjected to mastectomy. These data could be employed as a core in epigenetic-based data mining to establish a model for predicting the breast cancer-predisposed patients. However, further investigations are needed to fulfill this goal.

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