Browsing by Author "Bashtar, Abdel-Rahman"

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Abstract 4788: Detection of different genotypes of Human Cytomegalovirus in breast cancer patients.
(American Association for Cancer Research, 2013) Taha Mohamed, Hossam; El-Shinawi, Mohamed; Bashtar, Abdel-Rahman; Tarek abdel Salam, El-Said; J. Schneider, Robert; Mostafa Mohamed, Mona
Background: Human Cytomegalovirus (HCMV) is an endemic herpes virus that re-emerges in cancer patients enhancing oncogenic potential. Recent studies have shown that HCMV infection is associated with certain types of cancer morbidity such as glioblastoma; Although HCMV has been detected in breast cancer tissues. The ability of HCMV to infect diverse organs and cell types in vivo has been attributed to strain variations in certain genes of the virus. The relationship between genetic variants of the envelope glycoprotein genes of HCMV and disease outcome has been studied recently, among these variable genes HCMV ORF UL73 (envelope glycoprotein N). Aims: The aims of the present study were to 1) Screen for the infection of Human cytomegalovirus infection in inflammatory versus non-inflammatory breast cancer patients and 2) test the frequency of occurrence of multiple genotypes of HCMV glycoprotein N in IBC versus Non-IBC patients, to determine if there is any mixed infections by multiple genotypes in paired clinical specimens obtained from patients. Material and Methods: A total 93 (62 Non-IBC and 31 IBC) women diagnosed with breast cancer by clinical examination, ultrasound, mammography, and confirmed by biopsy (tru-cut) were enrolled into this study from Ain Shams university Hospitals. During modified radical mastectomy or conservative breast surgery carcinoma and non carcinoma tissues with peripheral blood were collected to detect the presence of Human cytomegalovirus DNA using nested PCR. HCMV glycoprotein N polymorphism (gN) was detected using multiplex PCR by using specific primers to each gN genotype which enable us to detect any mixed genotypes infection. Results: Analysis of the HCMV nested PCR to the carcinoma tissues showed that 63% of non-IBC carcinoma tissues were HCMV-DNA positive and 37% were HCMV-DNA negative. In IBC 80% of carcinoma tissues were HCMV-DNA positive and 20% were HCMV-DNA negative. Application of multiplex PCR for gN gene on HCMV positive carcinoma tissues (25 IBC and 32 Non-IBC) revealed that gN-1 genotype was detected in 25% of the non-IBC patients and 32% of the IBC patients, While gN-3b was detected in 6.25% of non-IBC patients and 4% of the IBC patients. Genotype gN-4a was detected in 9.38% of Non-IBC patients and in 4% of the IBC patients, while gN-4b\c was detected in 59.37% of Non-IBC patients and in 60% of the IBC patients. Also revealed mixed infection of gN-1+ gN-4b\c, gN-3b + gN-4b\c and gN-4a + gN-4b\c in Non-IBC patients and gN-1+ gN-4b\c, gN-3b + gN-4b\c in IBC patients. Conclusion: The frequency of HCMV infection in IBC was higher than Non-IBC patients; however the most dominant HCMV gN genotypes in IBC and Non-IBC are similar.
Inflammatory breast cancer: high incidence of detection of mixed human cytomegalovirus genotypes associated with disease pathogenesis
(Frontiers, 2014) Taha Mohamed, Hossam; El-Shinawi, Mohamed; Akram Nouh, M.; Bashtar, Abdel-Rahman; Tarek Elsayed, Elsayed; J. Schneider, Robert; Mostafa Mohamed, Mona
Inflammatory breast cancer (IBC) is a highly metastatic, aggressive, and fatal form of breast cancer. Patients presenting with IBC are characterized by a high number of axillary lymph node metastases. Recently, we found that IBC carcinoma tissues contain significantly higher levels of human cytomegalovirus (HCMV) DNA compared to other breast cancer tissues that may regulate cell signaling pathways. In fact, HCMV pathogenesis and clinical outcome can be statistically associated with multiple HCMV genotypes within IBC. Thus, in the present study, we established the incidence and types of HCMV genotypes present in carcinoma tissues of infected non-IBC versus IBC patients. We also assessed the correlation between detection of mixed genotypes of HCMV and disease progression. Genotyping of HCMV in carcinoma tissues revealed that glycoprotein B (gB)-1 and glycoprotein N (gN)-1 were the most prevalent HCMV genotypes in both non-IBC and IBC patients with no significant difference between patients groups. IBC carcinoma tissues, however, showed statistically significant higher incidence of detection of the gN-3b genotype compared to non-IBC patients. The incidence of detection of mixed genotypes of gB showed that gB-1 + gB-3 was statistically significantly higher in IBC than non-IBC patients. Similarly, the incidence of detection of mixed genotypes of gN showed that gN-1 + gN-3b and gN-3 + gN-4b/c were statistically significant higher in the carcinoma tissues of IBC than non-IBC. Mixed presence of different HCMV genotypes was found to be significantly correlated with the number of metastatic lymph nodes in non-IBC but not in IBC patients. In IBC, detection of mixed HCMV different genotypes significantly correlates with lymphovascular invasion and formation of dermal lymphatic emboli, which was not found in non-IBC patients.