Prognostic Significance of Combining Cytokeratin-19, E-Cadherin and Ki-67 Analysis in Triple-Negative Breast Cancer with Basal-Like and Non-Basal-Like Phenotype.

Triple-negative breast cancer (TNBC) is known to have the worst outcome compared to the other forms of breast cancer. Moreover, molecular markers identified basal-like breast cancer (BLBC) phenotypes to be also related to a worse prognosis. In this study, we evaluated by immunohistochemistry (IHC) the prognostic significance of combining Cytokeratin-19 (CK19), E-cadherin, and Ki-67 tissue expression in triple-negative breast cancer (TNBC) cases presenting a basal-like (BLBC) or a non-basal-like (n-BLBC) phenotype to improve the selection and the monitoring of BC patients with a more aggressive outcome.

Arginase is upregulated in healthy women infected by oncogenic HPV types.

Introduction: The implication of arginase enzyme in Human Papillomavirus (HPV) infections has not been clearly elucidated. The present study investigates whether HPV infection is correlated with changes in plasmatic arginase activity and cervical ARG1 and ARG2 mRNA expression among infected women negative for intraepithelial lesions (NIL).

Materiel And Methods: The present study included 300 women.

Indoleamine 2,3-dioxygenase gene expression and kynurenine to tryptophan ratio correlation with nasopharyngeal carcinoma progression and survival.

Introduction: Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive tryptophan-depleting enzyme expressed in nasopharyngeal carcinoma (NPC) tissue. However, IDO has not been reported in the peripheral blood of NPC patients. The aim of this study was to analyze, IDO1 and IDO2 messenger RNA (mRNA) expression, the kynurenine (Kyn) and tryptophan (Trp) plasma levels, their clinical values and their relationship with cytokine levels in NPC.

Arginase is involved in cervical lesions progression and severity.

Background: Little is known about the relationship between arginase, an immunosuppressive enzyme, and cervical lesions. The present study is aimed at evaluating arginase activity in plasma and mRNA arginase isoforms expression in cervical cells of patients with abnormal cytology and identifying their relationship with Human papillomavirus (HPV) related parameters such as: HPV type, HPV circulating viral load and anti-HPV16 IgG.

Methods: This study included 77 women with cervical lesions and 95 matched controls.

Human glutathione peroxidase codon 198 variant increases nasopharyngeal carcinoma risk and progression.

Purpose: Glutathione peroxidase 1 (GPx-1) is a selenium-dependent detoxifying enzyme involved in the protection of cells against oxidative damage. Some genetic association studies reported significant associations between GPx-1 Pro198Leu variant and carcinogenesis across different populations; however, the impact of this variant on nasopharyngeal carcinoma (NPC) has not been explored. Therefore, the present study was planned to evaluate the potential involvement of the GPx-1 Pro198Leu variant and plasma GPx activity in the risk of developing NPC in a Tunisian population.

Genetic Variation in CCL5 Signaling Genes and Triple Negative Breast Cancer: Susceptibility and Prognosis Implications.

Triple-negative breast cancer (TNBC) accounts for ~15-20% of breast cancer (BC) and has a higher rate of early relapse and mortality compared to other subtypes. The Chemokine (C-C motif) ligand 5 (CCL5) and its signaling pathway have been linked to TNBC. We aimed to investigate the susceptibility and prognostic implications of genetic variation in CCL5 signaling genes in TNBC in the present study.

Functional Polymorphisms and Gene Expression of TLR9 Gene as Protective Factors for Nasopharyngeal Carcinoma Severity and Progression.

Nasopharyngeal carcinoma (NPC) is a disease that is closely associated with EBV infection. Toll-like receptor 9 is an important factor mediating the interaction between EBV and the host immune response. Any genetic (single nucleotide polymorphisms, SNPs) or expression variation in TLR9 gene may modify the ability of the receptor to respond correctly to viral infection as in NPC.

Contribution of BRCA1 5382insC mutation in triple negative breast cancer in Tunisia.

Background: Triple negative breast cancer (TNBC) has been classified as a disease subgroup defined by the lack of expression of estrogen and progesterone receptors as well as the absence of the human epidermal growth factor receptor-2 (HER2) overexpression. Germline mutations in the BRCA1 gene have been associated with TNBC. Approximately 70% of breast cancers arising in BRCA1 mutation carriers and up to 23% of breast cancers in BRCA2 carriers display a triple negative phenotype.

Contribution of Nitric oxide synthase 3 genetic variants to nasopharyngeal carcinoma risk and progression in a Tunisian population.

Purpose: We conduct this study to evaluate the clinical and functional impact of Nitric Oxide Synthase 3 (NOS3) T-786C and G894T genetic variants on nasopharyngeal carcinoma (NPC) risk and progression in a Tunisian population.

Methods: 259 NPC patients and 169 healthy controls were enrolled into our case-control study. Blood samples were genotyped by the RFLP-PCR analysis.

E-cadherin genetic variants predict survival outcome in breast cancer patients.

Background: E-cadherin is a major component of adherens junctions that regulates cell shape and maintains tissue integrity. A complete loss or any decrease in cell surface expression of E-cadherin will interfere with the cell-to-cell junctions' strength and leads to cell detachment and escape from the primary tumor site. In this prospective study, three functional single nucleotide polymorphisms (-347G/GA, rs5030625; -160C/A, rs16260; +54C/T, rs1801026), were found to modulate E-cadherin expression.

Prognostic value of indoleamine 2,3-dioxygenase activity and expression in nasopharyngeal carcinoma.

Indoleamine 2,3-dioxygenase (IDO) is an enzyme with an immunosuppressive effect whose function is diverted by tumor cells to counteract immune cell functions, inducing immune escape of tumor cells. The aim of this study was to investigate the clinical significance of IDO in nasopharyngeal carcinoma (NPC). Compared to controls, NPC patients' plasma IDO activity was significantly higher, especially among patients with metastatic cancer (p=0.

Genome-Wide Association Studies (GWAS) breast cancer susceptibility loci in Arabs: susceptibility and prognostic implications in Tunisians.

Genome-wide Association Studies (GWAS) revealed novel genetic markers for breast cancer susceptibility. But little is known about the risk factors and molecular events associated with breast cancer in Arab Population. Therefore, we designed a broad study to investigate the susceptibility and prognostic implications of the GWAS breast cancer loci in the Tunisian population.

FASL-844 T/C polymorphism: a biomarker of good prognosis of breast cancer in the Tunisian population.

The single nucleotide polymorphism, rs763110 (-844 T/C) of the FASL gene, is located within a putative binding motif of CAAT/enhancer-binding protein β transcription factor. Higher basal expression of FASL is significantly associated with the FASL-844 C allele compared with the FASL-844 T allele suggesting that the FASL-844 T/C polymorphism may influence FASL expression and FASL-mediated signalling, and ultimately, the susceptibility to cancer. Therefore, we carried out a population-based study to estimate the FASL-844 C allele frequency in our population and to investigate, in a case-control study, the potential association of the FASL-844 T/C polymorphism with the risk and prognosis of breast cancer in Tunisia.

Hereditary breast cancer in Middle Eastern and North African (MENA) populations: identification of novel, recurrent and founder BRCA1 mutations in the Tunisian population.

Germ-line mutations in BRCA1 breast cancer susceptibility gene account for a large proportion of hereditary breast cancer families and show considerable ethnic and geographical variations. The contribution of BRCA1 mutations to hereditary breast cancer has not yet been thoroughly investigated in Middle Eastern and North African populations. In this study, 16 Tunisian high-risk breast cancer families were screened for germline mutations in the entire BRCA1 coding region and exon-intron boundaries using direct sequencing.

Epstein-Barr virus DNA quantification and follow-up in Tunisian nasopharyngeal carcinoma patients.

The prognostic value of the Epstein-Barr virus (EBV) DNA load in sera of nasopharyngeal carcinoma (NPC) patients measured before any treatment, after treatment and before relapse was assessed. The real-time polymerase chain reaction was used to detect the viral load levels among 74 NPC subjects. Patients were followed up for a period going from 1 to 6 years (median 4 years).

Combined effect of pro- and anti-inflammatory cytokine gene polymorphisms on susceptibility to liver cirrhosis in Tunisian HCV-infected patients.

Purpose: Chronic hepatitis C progression is commonly attributed to the continuous activation of the immune response with an increased production of pro-inflammatory cytokines, leading to fibrosis and ultimately to cirrhosis. On the contrary, anti-inflammatory cytokines, mainly interleukin (IL)-10 have a modulatory effect on hepatic fibrogenesis. The association between individual polymorphisms within cytokine genes and hepatitis C outcome is often weak and non-informative.

Lack of association between human leukocyte antigen-E alleles and nasopharyngeal carcinoma in Tunisians.

Nasopharyngeal carcinoma (NPC), a cancer with a remarkable geographical and worldwide ethnic distribution, has been strongly associated with human leukocyte antigen (HLA) class I genes. The presence of additional HLA risk factors has been suggested by several reports. In the present study, we analyzed the implication of HLA-E gene polymorphisms in NPC susceptibility in Tunisians, a population characterized by an intermediate incidence of NPC with specific clinical features.

Association of HLA-G polymorphisms with nasopharyngeal carcinoma risk and clinical outcome.

The expression of human leukocyte antigen-G (HLA-G) in tumor cells may facilitate the escape of the tumor from immunosurveillance; thus the aim of this study was to evaluate the influence of HLA-G polymorphisms occurrence on nasopharyngeal carcinoma (NPC) susceptibility, severity, and survival. Using the restriction fragment length polymorphism-polymerase chain reaction and the amplification refractory mutation system-polymerase chain reaction method, 186 Tunisian patients and 189 healthy controls were genotyped for nonsynonymous polymorphisms in HLA-G codon 31Thr/Ser, codon 110Leu/Ile and codon 130Leu/framshift. When allele, genotype and haplotype frequencies between patients and controls were compared for each single nucleotide polymorphisms (SNP), no statistical significant differences were observed.

Apolipoprotein A1 -75 G/A and +83 C/T polymorphisms: susceptibility and prognostic implications in breast cancer.

Apolipoprotein A1 (ApoA1) is the major apoprotein constituent of high-density lipoprotein that can play important roles in tumor invasion and metastasis. In the current report, we evaluated the role of the functional ApoA1 polymorphisms (-75 G/A and +83 C/T) as genetic markers for breast cancer susceptibility and prognosis. We used the polymerase chain reaction and restriction enzyme digestion (RFLP-PCR) to characterize the variations of the ApoA1 gene in 295 unrelated Tunisian patients with breast carcinoma and 197 healthy control subjects.

A single nucleotide polymorphism in the E-cadherin gene promoter -160 C/A is associated with risk of nasopharyngeal cancer.

Background: E-cadherin is a cell structural protein that has a pivotal role in cell-cell adhesion and epithelial development. Up to now, loss of activity of E-cadherin is believed to contribute to progression in several neoplastic diseases of epidermoid origin including nasopharyngeal carcinomas (NPC) by increasing invasion and proliferation. Besides, functional genetic variations in the promoter region of the E-cadherin gene have been associated with susceptibility to several neoplasms.

Combined analysis of interferon-gamma and interleukin-10 gene polymorphisms and chronic hepatitis C severity.

Today there is increasing evidence concerning the contribution of pro-/anti-inflammatory cytokine balance and genetic factors in hepatitis C pathogenesis and interindividual heterogeneity of disease outcome. In the current study, we investigated the influence of functionally described single nucleotide polymorphisms (SNPs) present in interferon-gamma (IFNgamma) and interleukin-10 (IL-10) genes, on chronic hepatitis C severity. IFNgamma (+874T/A) and IL-10 (-1082G/A) genotypes were determined in 100 hepatitis C patients with different disease severities (chronic hepatitis, n = 42, liver cirrhosis [LC], and hepatocellular carcinoma in liver cirrhosis [HCC], n = 58) and 103 healthy controls using allele-specific polymerase chain reaction.

Functional IL-18 promoter gene polymorphisms in Tunisian nasopharyngeal carcinoma patients.

Objectives: There is growing evidence suggesting that IL-18 levels may affect individual to virus-associated neoplasia and that single nucleotide polymorphisms (SNPs) within the gene may influence its production. In this study we wanted to know whether IL-18 polymorphisms at positions -607 C/A and -137 G/A are associated with susceptibility and/or are markers of nasopharyngeal carcinoma (NPC) prognosis.

Methods: Using the restriction fragment length polymerase chain reaction (RFLP-PCR), 163 Tunisian patients and 164 healthy controls were genotyped.

Implication of Xenobiotic Metabolizing Enzyme gene (CYP2E1, CYP2C19, CYP2D6, mEH and NAT2) polymorphisms in breast carcinoma.

Background: Xenobiotic Metabolizing Enzymes (XMEs) contribute to the detoxification of numerous cancer therapy-induced products. This study investigated the susceptibility and prognostic implications of the CYP2E1, CYP2C19, CYP2D6, mEH and NAT2 gene polymorphisms in breast carcinoma patients.

Methods: The authors used polymerase chain reaction and restriction enzyme digestion to characterize the variation of the CYP2E1, CYP2C19, CYP2D6, mEH and NAT2 gene in a total of 560 unrelated subjects (246 controls and 314 patients).

Matrix metalloproteinase-1 (-1607) 1G/2G and -9 (-1562) C/T promoter polymorphisms: susceptibility and prognostic implications in nasopharyngeal carcinomas.

Background: Matrix metalloproteinases (MMPs) are proteolytic enzymes that play important roles in tumor invasion and metastasis by degrading extracellular matrix components. Genetic variations in promoter regions of MMP genes, affecting their expression, have been associated with susceptibility to cancers. The aim of this study was to investigate the susceptibility and prognostic implications of the MMP-1 (-1607) 1G/2G and MMP-9 (-1562) C/T polymorphisms in nasopharyngeal carcinomas.

TAP1 gene polymorphisms and nasopharyngeal carcinoma risk in a Tunisian population.

To find out whether polymorphisms 333-Ile/Val and 637-Asp/Gly of the transporter part of the antigen processing 1 gene (TAP1) are associated with the development of nasopharyngeal carcinoma (NPC), we studied a total of 374 subjects (209 patients and 165 controls). We used the amplification refractory mutation system polymerase chain reaction (ARMS-PCR) method for analyzing the TAP1 gene polymorphisms. We found a significant difference between the patients and the controls in both the TAP1 codon 333 and codon 637 (P = 0.