Tumor DNA hypomethylation of LINE-1 is associated with low tumor grade of breast cancer in Tunisian patients.

DNA hypomethylation of long interspersed repetitive DNA retrotransposon (LINE-1) and Alu repeats elements of short interspersed elements family (SINEs) is an early event in carcinogenesis that causes transcriptional activation and leads to chromosomal instability. In the current study, DNA methylation levels of LINE-1 and Alu repeats were analyzed in tumoral tissues of invasive breast cancer in a Tunisian cohort and its association with the clinicopathological features of patients was defined. DNA methylation of LINE-1 and Alu repeats were analyzed using pyrosequencing in 61 invasive breast cancers. Median values observed for DNA methylation of LINE-1 and Alu repeats were considered as the cut-off (59.81 and 18.49%, respectively). The results of the current study demonstrated a positive correlation between DNA methylation levels of LINE-1 and Alu repeats (rho=0.284; P<0.03). DNA hypomethylation of LINE-1 was also indicated to be associated with low grade (P=0.023). To the best of our knowledge, the current study is the first study regarding DNA methylation of LINE-1 and Alu repeats element in breast cancer of the Tunisian population. The results of the current study suggest that, since hypomethylation of LINE-1 is associated with low grade, it could be used as a biomarker for prognosis for patients with breast cancer.

Clinicopathologic and Prognostic Significance of Gelatinase A in Tunisian Colorectal Cancer: A Case-Control Study.

Matrix metalloproteinase-2 (gelatinase A) is a well-known mediator of cancer metastasis, but it is also thought to be involved in several aspects of cancer development, including cell growth and inflammation. In the present study, we investigate whether MMP-2 SNP, MMP-2 mRNAs, and MMP-2 protein are associated with the susceptibility to colorectal cancer in the Tunisian population. The TaqMan allele discrimination assay and DNA sequencing techniques were used for genotyping; MMP-2 expression of each genotype was analyzed by semiquantitative RT-PCR, and MMP-2 protein expression was analyzed by immunohistochemistry staining. Our result showed that the levels of MMP-2 mRNA expression in patients containing the CC genotype were much higher compared with cells with the CT genotype. The frequency of the MMP-2 CC genotype was significantly higher in colorectal cancer patients when compared with controls (OR=1.94; 95% CI, 1.117-3.680). A higher intensity of staining of MMP-2 was observed in regions of invasion of the muscularis mucosa compared with superficial portions of the tumor. In addition, we found a significant progressive increase in total MMP-2 plasma levels with progression from adenomatous polyps through advancing Dukes stages (P=0.0001). Our data suggest that MMP-2 may be associated with colorectal cancer development and invasion in the Tunisian population; moreover, SNP and levels of MMP-2 could be a predictive value for colorectal cancer prevention and invasiveness.

Clinicopathologic and Prognostic Significance of Metalloproteinase Tissue Inhibitor-2 Promoters in Tunisian Colorectal Cancer: A Case-Control Study.

Tissue inhibitors of metalloproteinases (TIMPs) appear to affect many aspects of cancer biology, playing a crucial role in cell signaling by regulating cell growth, apoptosis, invasion, metastasis, angiogenesis, and genomic instability. In the present study, we investigate whether TIMP-2 SNP, TIMP-2 mRNAs, and TIMP-2 protein is associated with susceptibility to colorectal cancer (CRC) in Tunisian population. Taqman and DNA sequencing techniques were used for genotyping, TIMP-2 expression of each genotype was analyzed using semiquantitative RT-PCR and TIMP-2 protein expression was analyzed using immunohistochemistry staining. Our results showed that significantly elevated CRC risk was found in individuals with CC genotype (odds ratio 1.959; 95% confidence interval, 1.055-3.637). Moreover TIMP-2 mRNA expression in the colorectal cell carcinomas was significantly higher compared with the normal colorectal tissue (0.487±0.015 vs. 0.210±0.013) (P<0.05). In addition, serum levels of TIMP-2 were significantly lower in CRC patients than in adenoma patients (P=0.01) and healthy controls (P=0.003). Serum levels of TIMP-2 correlated significantly with tumor stage and TNM stage and were the lowest in CRC patients with stage D,T4,(N1,N2,N3),M(+). In conclusion, our study demonstrate for the first time the distribution and the clinical significance of TIMP-2 promoter polymorphisms, mRNA, protein expression, and serum level in CRC Tunisian patients suggesting that the genotyping and serum level of TIMP-2 as potential markers for susceptibility to CRC will allow a precise and early identification of individuals at high risk and will aid the design of therapeutic modalities and evaluation of treatment outcome.

Inferior vena cava leiomyosarcoma: vascular reconstruction is not always mandatory.

Leiomyosarcoma (LMS) of inferior vena cava is a rare and aggressive tumor, arising from the smooth muscle cells in the vessel wall. A large complete surgical resection is the essential treatment. The need of vascular reconstruction is not always mandatory. It's above all to understand the place of the reconstruction with artificial vascular patch prosthetics of vena cave after a large resection of the tumor. We rapport two cases of LMS of inferior vena cava in two women who underwent successful large resection of tumor and lower segment of inferior vena cava. In first case, reconstruction of the inferior vena cava was not performed because of the development of venous collaterals derivation. In the second case reconstruction was done using Dacron interposition graft. The necessity of a large resection in management of primary leiomyosarcoma of vena cave makes sometimes unavoidable the sacrifice of a portion of the vena. Indeed, a better comprehension of the development of venous derivation may render unnecessary the reconstruction.

Prognostic impact of polymorphism of matrix metalloproteinase-2 and metalloproteinase tissue inhibitor-2 promoters in breast cancer in Tunisia: case-control study.

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 matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) polymorphism in Tunisian breast cancer patients. MMP-2 genotypes were determined by real-time polymerase chain reaction (RT-PCR), and TIMP-2 genotypes were identified using a PCR-restriction fragment length polymorphism (RFLP) method in 210 breast cancer patients and 250 frequency-matched control women. Association of the clinicopathological parameters and the genetic markers with risk of breast cancer was assessed using univariate analyses. We found that the variant MMP-2 genotype (-1306CT or TT) was associated with substantially reduced risk of breast cancer [odds ratio (OR), 0.49; 95 % confidence interval (95 % CI), 0.033-0.73], compared with the CC genotype. For TIMP-2, a moderately reduced risk of the cancer (OR, 0.57; 95 % CI, 0.37-0.87) was also associated with the variant allele (-418GC or CC), compared with the GG common allele. Furthermore, polymorphisms in both genes seem to have additive effects and the highest risk for breast cancer has been observed in those with MMP-2 CC genotype and TIMP-2 GC or CC genotype (p = 0.006). A significant association was also found between the CC genotype and the aggressive forms of breast cancer as defined by advanced stages at the time of diagnosis and metastasis. This is the first report on the association of MMP-2 and TIMP-2 gene polymorphisms in breast cancer in Tunisian population. Our results suggest that the presence of the variant allele in the promoter of MMP-2 or TIMP-2 may be a protective factor for the development of breast cancer.

Head and neck liposarcomas: a 32 years experience.

OBJECTIVE: The aim of this review is to study natural history, presentation, treatment and prognosis of head and neck liposarcomas. METHODS: We carry a retrospective study about 15 patients diagnosed and treated in our department between 1969 and 2001. Therapeutic modalities included surgery, radiotherapy and chemotherapy. RESULTS: Tumors were mostly localized at the neck (4 cases) and the scalp (3 cases). Cervical lymphadenopathy was found in 1 case. Chest X-ray found showed metastases in 2 cases. Histological types of liposarcomas were the following: myxoid (5 cases), well differentiated (4 cases), pleomorphic (4 cases), round cell (1 case) and dedifferentiated (1 case). Twelve patients underwent surgery. Complete excision was performed in 7 cases. In the other 5 cases, exeresis was incomplete and 4 of them received postoperative radiotherapy. Three patients were not operated because of vascular involvement (1 case) or metastasis (2 cases), and they all received radiotherapy alone. After initial treatment, complete remission was achieved in 7 cases (46.7%). A recurrence occurred in 8 cases (53.3%). Two of these patients were reoperated and another one received chemotherapy. In the other 5 cases, the tumor was uncontrollable and no additional treatment has been proposed. Five-year survival rate was 87% for patients who underwent surgery alone, 75% for those who underwent surgery and postoperative radiotherapy, and 0% for those treated by radiotherapy alone. CONCLUSION: The mainstay of treatment of head and neck liposarcomas is surgical excision and the prognosis is largely determined by the histological grade and the clinical stage.