Salah Azeiz Oncology Institute

Tunis, Tunisia

Salah Azeiz Oncology Institute

Tunis, Tunisia

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Ben Hmida N.,Salah Azeiz Oncology Institute | Jebini S.,Salah Azeiz Oncology Institute | Mrad K.,Salah Azeiz Oncology Institute | Ben Romdhane K.,Salah Azeiz Oncology Institute
Disease Markers | Year: 2013

In an attempt to better unfold the antitumor immune response and invasion strategies perused by tumor cells, markers such as CD99 and HLA-II have been stained in breast tumors, some of them turned out to be important for prognosis and its outcome. CD99 is involved in the intracellular transport of HLA-II proteins. The expression of HLA-II and CD99 molecules has been demonstrated in a broader range of neoplastic tissues, including some epithelial tumors. In the present work, we stained CD99 and HLA-II in breast malignant and non-malignant tissues sections obtained from biopsies resected surgically from 80 Tunisian women. Data implied that CD99 marks malignant tissue significantly as compared to non-malignant breast tissue. HLA-II staining allowed determining the correlation between breast cancer and HLA-II with cytoplasmic localization. CD99 and HLA-II immunostaining was also examined in correlation with two of the most important breast cancer prognostication in routine clinical practice, the lymph node stage and the histological assessment. Results let suggest that CD99HLA-II is a marker of worst prognostic since this phenotype is strongly linked to lymph node metastasis in breast cancer. © 2013 - IOS Press and the authors. All rights reserved.


Zidi S.,Tunis el Manar University | Verdi H.,Baskent University | Yilmaz-Yalcin Y.,Baskent University | Yazici A.C.,Baskent University | And 4 more authors.
Pathology & Oncology Research | Year: 2014

Accumulative epidemiological evidence suggests that polymorphisms of cytokine genes and Toll-like receptors (TLR) signaling pathway elucidated the cellular and molecular mechanisms of human diseases, including cervical cancer, whose gaining a primordial importance. The aim of our study was to identify the role of TLR 2 (-196 to -174 del), TLR 3 (1377 C > T), TLR 4 (Asp299Gly), TLR 9 (G2848A), IL1-α (4845 G > T), IL-1β (-511C > T) and TNF-α (-238 G > A) gene polymorphisms with cervical cancer susceptibility in Tunisian women. Blood samples were collected from histopathologically confirmed patients with cervical cancer (n = 130) and unrelated healthy female controls of similar ethnicity (n = 200). Genomic DNA was extracted from peripheral blood leukocytes using QIAamp® DNA blood Mini Kit method. Genotyping of the analyzed polymorphisms were done using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism. For the TLR3 (1377 C > T) polymorphism, the OR for patients with C/T vs C/C genotype was 2.00 (95 % CI: 1.22-3.31; p = 0.0036) and the OR of C/T + T/T vs C/C genotype was 1.85 (95 % CI: 1.15-2.96; p = 0.0070). For TLR4 (Asp299Gly), the Asp allele and Asp/Asp genotype are associated with higher risk of developing CC: the allelic comparison Asp vs Gly was (OR: 5.70, 95 % CI: 3.44-9.52), for the genotypic comparison Asp/Asp vs Asp/Gly, vs Gly/Gly and vs Asp/Gly + Gly/Gly was respectively; (OR: 11.99, 95%CI: 4.73-32.21) (OR: 5.51, 95 % CI: 2.33-13.47) and (OR: 8.29, 95 % CI: 4.30-16.20) . For IL-1β (-511), the OR for patients with T/T vs C/C genotype was 5.33 (95 % CI: 2.15-13.45; p = 0.0000) and the OR of combined C/T + T/T vs C/C genotype was 1.77 (95 % CI: 0.98-3.22; p = 0.0430). Our study suggests that the TLR3 (1377 C > T), TLR4 (Asp299Gly), and IL-1β (-511C > T) polymorphisms may be a genetic risk factor for cervical cancer. © 2014 Arányi Lajos Foundation.


Zidi S.,Tunis el Manar University | Gazouani E.,Military Hospital of Tunis | Stayoussef M.,University of Monastir | Mezlini A.,Salah Azeiz Oncology Institute | And 3 more authors.
Cytokine | Year: 2015

Objective: We investigated the association between polymorphisms in the promoter and intron regions of the interleukin-10 (IL-10) gene with the risk of cervical cancer (CC) in Tunisian patients and control women. Methods: Study subjects comprised 86 CC cases and 126 control women. Genotyping of IL-10 intron (rs3024491, rs3024490) and promoter (rs1800872, rs1800871, rs1800896) variants was done by real-time PCR, with defined clusters. Results: The minor allele frequencies of the five tested IL-10 SNPs were not significantly different between cervical cancer cases and control women. However, significantly higher frequencies of homozygous minor allele-carriers in cases was seen for rs3024490 (P=0.023), rs1800872 (P=0.037), and rs1800871 (P=0.028). IL-10 serum levels were significantly reduced in rs3024490 T/T vs. G/G genotype carriers, and in rs1800871 T/T than C/C genotype carriers. While carriage of rs1800872 and rs3024491 minor allele was associated with reduced IL-10 secretion, this was not statistically significant. Haploview analysis demonstrated high linkage disequilibrium (LD) among the IL10 SNPs studied, and only seven haplotypes were common, capturing 98.8% of the total possible haplotypes. Reduced frequency of haplotypes GTCCA (P<0.001) and TGATG (P<0.001) was seen in cervical cancer cases than in control women, thus conferring disease protection nature to these haplotype. This association remained significant for GTCCA (Pc=0.006) and TGATG (P=0.045) after correcting for multiple comparisons. Conclusion: Specific IL-10 variants (rs3024490, rs1800872, and rs1800871) and haplotype (GTCCA and TGATG) may contribute to the development of cervical cancer among Tunisian women. © 2015 Elsevier Ltd.


Zidi S.,Tunis el Manar University | Stayoussef M.,University of Monastir | Gazouani E.,Military Hospital of Tunis | Mezlini A.,Salah Azeiz Oncology Institute | And 2 more authors.
Cytokine | Year: 2015

Objective: We investigated the association between common vascular endothelial growth factor (. VEGF) single nucleotide polymorphisms (SNPs) and the risk of cervical cancer (CC) in Tunisian patients and control women. Methods: Study subjects comprised 86 CC cases and 124 control women. Genotyping of VEGF rs699947, rs833061, rs1570360, rs2010963, rs25648, rs833068, rs833070, rs3025039 SNPs was done by real-time PCR. Results: Higher minor allele frequencies (MAF) of rs699947 (-2578C/A) [P=0.04; OR (95% CI)=1.52 (1.02-2.29)], and rs1570360 (-1154G/A) [P=0.04; OR (95% CI)=1.58 (1.01-2.47)] were seen in CC cases compared to control women. Marked differences in the distribution of rs699947 (P=9×10-4) and rs1570360 (P=0.03) genotypes were seen between CC cases and control groups; the distribution of the remaining SNPs was comparable between CC cases and control women. The association of rs699947 and rs1570360 with heightened CC risk with was seen in the heterozygous, and more so in the homozygous states. Haploview analysis revealed high LD between rs699947, rs833061, rs1570360, rs2010963, rs25648, rs833068 and rs833070 but weak or no LD between rs3025039 and the other SNPs. Seven-locus (rs699947/rs833061/rs1570360/rs2010963/rs25648/rs833068/ rs833070) haploview analysis identified only CTGCCAG haplotype to be positively associated with CC [P=0.022; OR(95% CI)=1.74 (1.08-2.79)]. Conclusion: Specific VEGF variants (rs699947, rs1570360) and haplotype (CTGCCAG) may contribute to the development of CC among Tunisian women. © 2014 Elsevier Ltd.


PubMed | Tunis el Manar University, Military Hospital of Tunis, Arabian Gulf University and Salah Azeiz Oncology Institute
Type: | Journal: Pathology oncology research : POR | Year: 2016

For the first time in the word, we investigated the association between five FSHR polymorphisms with the risk of cervical cancer among Tunisians. Study subjects comprised 112 Cervical Cancer (CC) patients and 164 control women. Genotyping of FSHR rs6166, rs1007541, rs11692782, rs2055571 and rs1394205 variants was done by realtime PCR, with defined clusters. The allelic distributions of the tested FSHR SNPs were comparable between CC patients and control women. In contrast, the heterozygous genotype of rs1007541 was associated with 1.8-fold increased risk of CC. Stratification according to FIGO staging revealed that the minor allele of rs1007541 was more frequent among advanced tumor stage patients, with 11-fold increased risk of CC [P<0.0001; OR (95% CI)=11.32 (7.46-17.18)]. However, no significant allelic association was revealed in the rest of analyzed FSHR SNPs. Haploview analysis showed high Linkage disequilibrium (LD) between rs2055571 and rs1394205. Haplotype analysis revealed a lack of association between cases and controls. However, analysis of CC patient subgroups demonstrated enrichment of GGTAG haplotype in early tumor stage [P=0.025; OR (95% CI)=0.07 (0.01-0.70)]. The FSHR variants and haplotypes may be a genetic markers for CC susceptibility and evolution among Tunisian women.


PubMed | Tunis el Manar University, Military Hospital of Tunis, University of Monastir, Salah Azeiz Oncology Institute and Arabian Gulf University
Type: Journal Article | Journal: Cytokine | Year: 2015

We investigated the association between polymorphisms in the promoter and intron regions of the interleukin-10 (IL-10) gene with the risk of cervical cancer (CC) in Tunisian patients and control women.Study subjects comprised 86 CC cases and 126 control women. Genotyping of IL-10 intron (rs3024491, rs3024490) and promoter (rs1800872, rs1800871, rs1800896) variants was done by real-time PCR, with defined clusters.The minor allele frequencies of the five tested IL-10 SNPs were not significantly different between cervical cancer cases and control women. However, significantly higher frequencies of homozygous minor allele-carriers in cases was seen for rs3024490 (P=0.023), rs1800872 (P=0.037), and rs1800871 (P=0.028). IL-10 serum levels were significantly reduced in rs3024490 T/T vs. G/G genotype carriers, and in rs1800871 T/T than C/C genotype carriers. While carriage of rs1800872 and rs3024491 minor allele was associated with reduced IL-10 secretion, this was not statistically significant. Haploview analysis demonstrated high linkage disequilibrium (LD) among the IL10 SNPs studied, and only seven haplotypes were common, capturing 98.8% of the total possible haplotypes. Reduced frequency of haplotypes GTCCA (P<0.001) and TGATG (P<0.001) was seen in cervical cancer cases than in control women, thus conferring disease protection nature to these haplotype. This association remained significant for GTCCA (Pc=0.006) and TGATG (P=0.045) after correcting for multiple comparisons.Specific IL-10 variants (rs3024490, rs1800872, and rs1800871) and haplotype (GTCCA and TGATG) may contribute to the development of cervical cancer among Tunisian women.


PubMed | Tunis el Manar University, Military Hospital of Tunis, Arabian Gulf University and Salah Azeiz Oncology Institute
Type: | Journal: Pathology oncology research : POR | Year: 2016

We investigated the association between six common and novel interleukin-6 (IL-6) polymorphisms with the risk of cervical cancer (CC) among Tunisians. Study subjects comprised 112 CC cases and 164 control women. Genotyping of IL-6 rs2069845, rs2069840, rs1474348, rs1800795, rs1800797, rs2069827 variants was done by real-time PCR, with defined clusters. The allelic and genotypic distributions of the tested IL-6 SNPs were comparable between CC patients and control women. Stratification according to FIGO staging revealed that rs1800795 homozygous major allele genotype (P=0.033; OR =0.49(0.25-0.95)) and major allele (P=0.037; OR=0.57 (0.33-0.97)) were protective of CC. Moreover, carriage of rs1474348 major allele was also protective of CC (P=0.014; OR=0.53(0.32-0.88)), while higher rs1474348 minor allele frequency was seen in CC patients with early FIGO stage (P=0.044; OR=0.39 (0.15-1.00)), thus implicating rs1474348 in CC evolution and progression of angiogenesis. Haploview analysis demonstrated high linkage disequilibrium (LD) between rs2069845, rs2069840, rs1474348 and rs1800795, and 6-locus haplotype analysis identified GACCCA haplotype to be positively associated with increased CC, while GAGGGG haplotype was negatively associated with CC, thus suggesting a protective role for this haplotype in CC. Furthermore, there was a significant association between the incidence of CC and the use hormonal contraception (P=0.047; OR=1.97 (0.94-4.13)) and smoking (P<0.001; OR=7.12 (2.97-17.04)). The IL-6 variants rs1800795 and rs1474348, and haplotypes GACCCA and GAGGGG, along with use of hormonal contraceptives and smoking, are major risk factors of CC susceptibility and evolution among Tunisian women.


Zidi S.,Tunis el Manar University | Sghaier I.,Tunis el Manar University | Gazouani E.,Military Hospital of Tunis | Mezlini A.,Salah Azeiz Oncology Institute | Yacoubi-Loueslati B.,Tunis el Manar University
Pathology and Oncology Research | Year: 2015

Accumulative epidemiological evidence suggests that polymorphisms of Toll-like receptors signaling pathway elucidated the cellular and molecular mechanisms of human diseases whose gaining a primordial importance. The aim of our study is to identify the role of TLR 2 (−196 to −174 del), TLR 3 (1377 C>T), TLR 4 (Asp299Gly) and TLR 9 (G2848A) gene polymorphisms with the evolution of cervical cancer in Tunisian women. Blood samples were collected from histopathologically confirmed patients with cervical cancer and unrelated healthy female controls of similar ethnicity. Genotyping of the analyzed polymorphisms were done using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism. For the TLR 2, Ins/Ins genotype is a protector factor [p = 0.006; OR: 0.35(0.16–0.73)] and the dominant genotype of TLR 3 increased the risk of CC in stage (III+IV); C/C versuss C/T [p = 0.033; OR: 2.03(1.00–4.13)] and C/C versus C/T+T/T [p = 0.036; OR: 1.93(1.00–3.74)]. For TLR 4, the dominant genotype Asp/Asp is implicated in the occurrence of CC in stage (I+II) [p = 0.000; OR: 4.55(1.58–13.06)], [p = 0.001; OR: 3.49(1.44–8.45)] and in stage (III+IV) [p = 0.038; OR: 3.77(0.87–16.29)], [p = 0.007; OR: 5.21(1.65–16.46)] and the major allele Asp is a risk factor for the development of tumor in stage (I+II). The TLR2 Ins/Del genotype is associated with tumor evolution to stage (III+IV) [p = 0.003; OR: 3.00 (1.22–7.35)] and the genotypes Gly/Gly and Asp/Gly+Gly/Gly and Gly allele of TLR 4 are implicated in tumor evolution to the advanced stages. Further, TLR 2, TLR 3, TLR 4 and TLR 9 gene polymorphisms are implicated in the modulation of CC risk due to tobacco usage and statue of menopause among cases. Our study suggests a relationship between the incidence of the TLR2, TLR 3, TLR 4 and TLR9 mutations and the clinical progression of CC according to the FIGO classification. However, future studies with different demographic and clinical characteristics in ethnically diverse populations may provide a more comprehensive involvement of innate immunity in cervical cancer etiology in women worldwide. © 2015 Arányi Lajos Foundation


Ben Othmane Y.,Tunis el Manar University | Ghazouani E.,Military Hospital of Tunis | Mezlini A.,Salah Azeiz Oncology Institute | Lagha A.,Military Hospital of Tunis | And 7 more authors.
Bulletin du Cancer | Year: 2012

The variability in host immunogenetic background, especially in human major histocompatibilty genes, has been shown to influence the susceptibility to human papillomavirus (HPV) infection and cervical neoplasia. Here, we conducted a case-control study in Tunisian women to examine the effect of genetic variation in HLA class II DRB1 and DQB1 genes on invasive cervical cancer (ICC) and squamous cell carcinoma (SCC). HLA genotyping was performed by PCR sequence-specific primers technique. The data revealed significant positive and negative associations, suggesting either predisposing or protective effects of these genes in the disease outcome. DRB1*15, alone or linked to DQB1*06, was associated with a 2.7- and 3.5-fold increase in risk for ICC, respectively. DRB1*13-DQB1*03 showed a similar 3.5 risk effect. Concerning SCC, we observed a relatively higher, about 1.2 times more, risk effect for these genetic markers. In contrast, only one haplotype - DRB1*13-DQB1*06 - provides evidence for a weak protection (about 0.3-fold reduction) of ICC and SCC. In conclusion, we suggest that HLA class II polymorphisms are involved in the genetic susceptibility to cervical cancer in Tunisian women.


PubMed | Tunis el Manar University, Military Hospital of Tunis and Salah Azeiz Oncology Institute
Type: Journal Article | Journal: Pathology oncology research : POR | Year: 2016

Accumulative epidemiological evidence suggests that polymorphisms of Toll-like receptors signaling pathway elucidated the cellular and molecular mechanisms of human diseases whose gaining a primordial importance. The aim of our study is to identify the role of TLR 2 (-196 to -174 del), TLR 3 (1377 C>T), TLR 4 (Asp299Gly) and TLR 9 (G2848A) gene polymorphisms with the evolution of cervical cancer in Tunisian women. Blood samples were collected from histopathologically confirmed patients with cervical cancer and unrelated healthy female controls of similar ethnicity. Genotyping of the analyzed polymorphisms were done using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism. For the TLR 2, Ins/Ins genotype is a protector factor [p = 0.006; OR: 0.35(0.16-0.73)] and the dominant genotype of TLR 3 increased the risk of CC in stage (III+IV); C/C versus C/T [p = 0.033; OR: 2.03(1.00-4.13)] and C/C versus C/T+T/T [p = 0.036; OR: 1.93(1.00-3.74)]. For TLR 4, the dominant genotype Asp/Asp is implicated in the occurrence of CC in stage (I+II) [p = 0.000; OR: 4.55(1.58-13.06)], [p = 0.001; OR: 3.49(1.44-8.45)] and in stage (III+IV) [p = 0.038; OR: 3.77(0.87-16.29)], [p = 0.007; OR: 5.21(1.65-16.46)] and the major allele Asp is a risk factor for the development of tumor in stage (I+II). The TLR2 Ins/Del genotype is associated with tumor evolution to stage (III+IV) [p = 0.003; OR: 3.00 (1.22-7.35)] and the genotypes Gly/Gly and Asp/Gly+Gly/Gly and Gly allele of TLR 4 are implicated in tumor evolution to the advanced stages. Further, TLR 2, TLR 3, TLR 4 and TLR 9 gene polymorphisms are implicated in the modulation of CC risk due to tobacco usage and statue of menopause among cases. Our study suggests a relationship between the incidence of the TLR2, TLR 3, TLR 4 and TLR9 mutations and the clinical progression of CC according to the FIGO classification. However, future studies with different demographic and clinical characteristics in ethnically diverse populations may provide a more comprehensive involvement of innate immunity in cervical cancer etiology in women worldwide.

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