Biljana Jekic

Cancer genes alterations and HPV infection in oral squamous cell carcinoma

The aim of this study was to gain a better understanding of cancer genes contributing to oral squamous cell (OSCC) development and progression and correlate genetic changes to clinical parameters. Human papilloma virus (HPV) 16 detection is also included in the study. 60 samples of OSCC were analysed for c-erbB2 and c-myc amplification by dPCR, H-ras and p53 point mutations by PCR/SSCP. HPV was detected via amplification of its E1 and E6 genes. c-erbB2 was altered in 45%, c-myc in 35%, H-ras in 22% and p53 in 60% of samples. HPV was detected in 10% of cases. The frequency of p53 gene mutations showed a statistically significant association with tumour stage. Patients with c-erbB2 and H-ras alterations had lower survival than patients without these alterations. The number of detected genetic changes was remarkable but statistical association with tumour natural history was poor, indicating high clonal heterogeneity and multiple pathways of carcinogenesis.

Association between the methylenetetrahydrofolate reductase polymorphisms and risk of acute lymphoblastic leukemia in Serbian children.

Methylenetetrahydrofolate reductase (MTHFR) regulates the metabolism of folate and methionine, essential components of DNA synthesis and methylation. Polymorphisms in the MTHFR gene have been associated with susceptibility to some types of cancer. We investigated a possible association of MTHFR polymorphisms (677C>T and 1298A>C) and increased risk for acute lymphoblastic leukemia in 78 affected children. The frequencies of both MTHFR 677 genotypes and alleles were significantly different between patients and controls. A significant association between CT/TT individuals and reduced risk of acute lymphoblastic leukemia was found. The odds ratios were 0.53 (95% confidence interval, 032-0.89) and 0.30 (95% confidence interval, 0.12-0.81). Polymorphism 1298 did not show statistical difference between patients and controls.

Bcl-2 Expression in Oral Squamous Cell Carcinoma

Abstract:  Apoptosis is a genetically regulated process involved in tissue size regulation, morphogenesis, and elimination of genetically damaged cells. A pallet of genes is involved in the control of apoptosis, such as bcl‐2 family whose oncogenic potential has been demonstrated in oral tumorigenesis. Different members of bcl‐2 family may promote or inhibit apoptosis by synthesizing anti‐ and proapoptotic proteins. One of antiapoptotic proteins, bcl‐2, with a crucial role in apoptosis regulation was the object of our study. By means of immunohistochemistry we estimated the level of overexpression of bcl‐2 proteins in a series of the 26 formalin fixed, paraffin‐embedded samples of oral squamous cell carcinoma (OSCC). Analyzed tumors originated from different sites of oral cavity; 7/26 belonged to stage II, 14/26 to stage III, and 5/26 to stage IV. Immunoreactivity was scored according to the percentage and intensity of positive cytoplasmic bcl‐2 staining. All tumors had low percentage of positively stained bcl‐2 cells, with mean values for lower/higher intensity of 8.3 ± 2.5/34.4 ± 7, 7.5 ± 1.1/31.9 ± 4.3, and 8.4 ± 5.8/31.5 ± 5.8 within stages II, III, and IV, respectively. Low level of bcl‐2 expression in our sample seems to be associated with higher survival rate: 77% for the 5‐year follow‐up period. Comparing clinicopathologic and risk factors data within each and between three groups of analyzed tumors (lip–tongue P= 0.58, tongue–floor of the mouth, P= 0.21, lip–floor of the mouth, P= 0.50) there was no significant difference. However, our results suggest that the level of bcl‐2 expression could be a valuable predictor of tumor behavior and disease outcome.

Large Cell Lung Carcinoma with Unusual Imaging Feature, Immunophenotype and Genetic Finding

We present a case of large cell lung carcinoma in sixty-one year old male with typical lung cancer symptoms but unusual radiological presentation and immunophenotype. Tumor morphological finding related to its radiological finding was suggestive for large cell lymphoma or carcinoma, but its immunophenotype made confusion for pathological diagnosis. No p53 mutations were detected in genetic investigation. Multidisciplinar diagnostic approach to some tumors is useful for their final diagnosis.

Degree of genetic homozygosity and distribution of AB0 blood types among patients with spina bifida occulta and spina bifida aperta

Introduction Assuming that spina bifida (SB) is a genetically controlled disease, the aim of our study was to evaluate the degree of genetic homozygosity and the distribution of AB0 blood types among patients with SB occulta and SB aperta by the homozygously recessive characteristics (HRC) test. Material and methods Our study included an analysis of the presence, distribution and individual combination of 15 selected genetically controlled morpho-physiological traits in a sample of 100 patients with SB (SB occulta N = 50 and SB aperta N = 50) and a control group of individuals (N = 100). Results We found a statistically significant difference between the mean values for genetic homozygosity (SB 4.5 ±0.3; control 3.0 ±0.2, p < 0.001) and also differences in the presence of certain individual combinations of such traits. In 12 (80.0%) of the 15 observed characteristics, recessive homozygosity was expressed to a greater degree among the group of SB patients, while for 9 (60.0%) of the traits this level of difference was statistically significant (Σχ 2 = 266.3, p < 0.001). There was no difference in average homozygosity of such genetic markers between groups of SB occulta and SB aperta patients, but the type of individual variation in the two studied groups significantly differed. In the group of patients with SB the frequency of 0 blood group was significantly increased while B blood group was significantly decreased. Conclusions Our results clearly show that there is a populational genetic difference in the degree of genetic homozygosity and variability between the group of patients with SB and individuals without clinical manifestations, indicating a possible genetic component in the aetiopathogenesis of spina bifida.

Polymorphisms of the eNOS gene are associated with disease activity in rheumatoid arthritis

Nitric oxide (NO) is a mediator in autoimmune responses and thus involved in the pathogenesis of a variety of rheumatic diseases. Genetic factors that influence the expression of the enzyme endothelial nitric oxide synthase (eNOS) that catalyzes NO synthesis are important for the control of NO level and consequently its activity. We have analyzed three functionally relevant polymorphisms of eNOS gene: T-786C, G894T and VNTR (4a/b), to investigate whether they are predisposing factors in pathogenesis of RA in Serbian population and to evaluate their role in clinical manifestations of RA. We performed genotyping of 196 patients with RA and the control group of 132 healthy individuals from Serbian population, using PCR and polymerase chain reaction–restriction fragment length polymorphism methods. Disease activity was prospectively assessed using number of tender joints, number of swollen joints and 28-joints disease activity score (DAS28). There were no differences between the patients and control groups in the genotypes and alleles frequencies of the three analyzed SNPs. Our results showed statistically significant differences in all three analyzed parameters of disease severity between 786TT/786CT and 786CC genotypes and between 894GG/894GT and 894TT genotypes. In the case of 4a/b polymorphism, carriers of minor allele had significantly lower DAS28 values. In conclusion, our results do not support the implication of analyzed eNOS gene polymorphisms in susceptibility to RA but associate them with the disease activity and give assumption that minor alleles are indicators of better clinical course.

Anthropogenetic Variability in the Group of Individuals with Febrile Seizures: Population-Genetic Study

Febrile seizures (FS) are the most common neurological disorder in childhood and are a great stress for parents due to their dramatic clinical appearance. Using test for determination of homozygously recessive characteristics in humans (HRC test) we analyzed presence, distribution, and individual combination of 20 selected genetically controlled morphophysiological traits among FS patients (N=121) and control (N=121) to determine a possible deviation in the homozygosity level and genetic loads in the group of affected children and whether there is a predisposition to the occurrence of FS. The results of our study show a statistically significant difference in the mean values of the HRC tested (x¯HRC/20 CN = 3.2 ± 0.2; x¯HRC/20 FS = 4.6 ± 0.2, t= 5.74 , p< 0.0001), as well as in the distribution and variability of two studied samples (VC=55,3%, VFS= 39,6%), which indicates a complex polygenic difference among the tested groups of subjects. The differences in the degree of genetic homozygosity and variability are also present between the genders (t Cf/FSf = 4.12; t Cm/FSm = 3.98; p <0.0001) (VCf=56.9%, VFSf= 39.3%; VCm=54.1%, VFSm=40.1%). Obtained results indicate the enlargement of recessively homozygous genetic loads in the group of children with FS which may represent some kind of predisposition for expressivity of this type of seizures.