microRNAs expression profile in phyllodes tumors of the breast

Proliferation of both stromal and epithelial components is a characteristic of fibroepithelial cancers of the breast. Certain fibroepithelial tumors of the breast, such as fibradenomas and phyllodes tumors, are challenging to distinguish and categorize. To find biomarkers for early diagnosis and improved disease management, it is crucial to deepen our understanding of the molecular pathogenesis pathways and tumor biology of PTs. It has been demonstrated that microRNAs (miRNAs) have significant roles in cancers; the expression pattern of miRNAs can help with cancer categorization and treatment. In contrast, little is understood about miRNAs in breast fibroepithelial cancers.This study was conducted retrospectively with the goal of assessing the expression of six mature miRNAs (hsa-miR-21, hsa-miR-155, hsa-miR-182, hsa-miR-34a, hsa-miR-148a, and hsa-miR-205) in breast fibroepithelial cancers using real-time PCR and predicting these miRNAs' targets using computational techniques.This study comprised 64 patients in total—55 with phyllodes tumors and 9 with fibroadenoma. The research was carried out at the Farhat Hached University Hospital's pathology department in Tunisia. These particular miRNAs expression levels were evaluated via qRT-PCR, and in silico techniques were utilized to predict potential miRNA targets.Analysis of miRNA expression in fibroadenoma and phyllodes tumor tissues revealed that miR-21, miR-155 and miR-182 were upregulated in PTs compared to fibroadenoma and normal tissues. We reported that miR-34a, miR-148a and miR-205 were downregulated in both borderline and malignant PTs compared to fibroadenoma and normal tissue. In silico miRNA target prediction suggested the involvement of these molecules in a wide context of cell signaling pathways

Contribution de l’inactivation épigénétique des gènes BRCA1 et BRCA2 dans les cancers du sein sporadiques en Tunisie

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Investigation of allelic imbalances on chromosome 3p in nasopharyngeal carcinoma in Tunisia: high frequency of microsatellite instability in patients with early-onset of the disease

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No evidence of human papillomavirus DNA in breast carcinoma in Tunisian patients

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Investigation of Epstein-Barr virus in Tunisian breast carcinomas

peer reviewedBreast carcinoma is a major cause of death among women, and the potential implication of viruses in its pathogenesis remains worth a hypothesis. The potential role of Epstein-Barr virus (EBV) in its pathogenesis is still a subject of continued discussion and investigation. The aim of this study was to evaluate the prevalence of EBV in sporadic breast cancers in Tunisia, and to determine the clinicopathological characteristics of virus-positive cases. Viral presence has been evaluated by polymerase chain reaction (PCR), in situ hybridization, and immunohistochemistry investigated on tumor tissues and their corresponding normal breast tissues collected from 123 Tunisian women with sporadic breast carcinomas. Viral status in tumors was then correlated with various clinicopathological parameters. Using specific PCR assays, EBV DNA was found in 33 (27%) out of 123 breast carcinoma cases. EBV-encoded small RNAs (EBERs) in situ hybridization was negative in the neoplastic cells, but stomal lymphocytes were positive in 4 cases. Immunohistochemistry for latent membrane protein 1 (LMP1) was negative in all cases. None of the normal breast tissues showed positive results for EBV using PCR, in situ hybridization, and immunohistochemistry. A correlation was found between EBV DNA presence and the negativity of estrogen receptor (P=0.008). However, no significant correlation was found for the other parameters investigated, including patient age, Scarff-Bloom-Richardson (SBR) histological grade, tumor size, and histological node involvement. With regard to survival data, overall and disease-free survivals were shorter in EBV-positive breast carcinoma cases than in EBV-negative ones, but this difference did not reach statistical significance. Our study indicates the presence of EBV DNA in a significant proportion of breast cancer in Tunisia. Further studies are required to elucidate the role of this virus in breast carcinogenesis

Investigation of human JC and BK polyomaviruses in breast carcinomas

We have previously showed the presence of the simian virus 40 (SV40) and the mouse mammary tumor virus (MMTV)-like in a significant proportions of Tunisian breast carcinomas. However, to date there are no published studies concerning evaluation of the possible implication of the human polyomaviruses JC (JCV) and BK (BKV) in breast carcinomas. The presence of JCV and BKV DNA was investigated by PCR in a 123 primary breast carcinomas and matched adjacent non-tumor breast tissues. The results were correlated to clinicopathological and virological parameters. JCV T-antigen DNA was detected in 23% of breast carcinoma cases; however, all cases were negative for BKV. JCV T antigen PCR products were further confirmed as authentic JCV genome by direct sequencing. JCV was found in invasive ductal carcinomas (28/112 cases) but not in invasive lobular carcinomas (0/5) or medullary carcinomas (0/6). JCV DNA presence correlates inversely with the expression of estrogen (P = 0.022) and progesterone (P = 0.008) receptors. JCV DNA presence correlates also with "triple negative" phenotype (P = 0.021). With regard to virological data, a trend toward an inverse correlation was noted between the presence of JCV and SV40 (P = 0.06). Moreover, significant correlation was found between multiple viral infection (JCV, and/or SV40, and/or MMTV-like in the same tumor) and "triple negative" phenotype (P = 0.001) and also with p53 accumulation (P = 0.028). To the best of our knowledge, this is the first study demonstrating the presence of JCV in a subset of breast carcinomas. Also our results suggest that "triple negative" breast carcinomas are viral-related tumors

Contribution of epigenetic alteration of BRCA1 and BRCA2 genes in breast carcinomas in Tunisian patients

Objective: The aim of this study was to evaluate the contribution of the BRCA1 and BRCA2 promoter methylation in the pathogenesis of sporadic breast cancer in Tunisian patients. Methods: Breast carcinoma tissues (n=117) and available paired normal breast tissues (n=65) from Tunisian women who had no family history were investigated for the methylation status of BRCA1 and BRCA2 promoters using methylation-specific PCR. Breast specimens from women without carcinoma (16 fibroadenomas and 5 mastopathies) were used as control. Results: Hypermethylation of BRCA1 and BRCA2 promoters was detected respectively in 60.7% and 69.2% of the carcinoma tissues, and in only 7.7% and 4.6% of the paired normal breast tissues. None of the fibroadenomas and mastopathies showed hypermethylation. Correlations were found between BRCA1 and BRCA2 hypermethylation and decrease in their mRNA expression (p=0.02 and p=0.009, respectively). Moreover, BRCA1 methylation correlates with patients age (p=0.01) and triple negative (ER-, PR-, HER2-) tumors (p=0.01). Patients with methylated BRCA1 and/or BRCA2 had a significant prolonged survivals compared to those with unmethylated tumors (p=0.002). Conclusion: Our results suggest an important role of BRCA1 and BRCA2 promoter methylation in breast cancer development in the Tunisian population