فهرست مطالب دکترمهدی نیکبخت دستجردی

Various tumor suppressor genes play a role in colorectal cancer; the role of breast cancer 1 (BRCA1) tumor suppressor gene is of the most importance among them. The biological performance of breast cancer 1 (BRCA1) in cancer has been recognized and its prognostic significance has been verified in colorectal cancer; decrease in the expression of this protein in cancer indicates a poor prognosis for patients. The aim of the current study was to evaluate BRCA1 protein expression in cancerous colorectal specimens compared to healthy tissue surrounding the tumor using immunohistochemistry method.
A total of 50 cancerous colorectal and 50 healthy specimens were collected. The expression of BRCA1 protein was evaluated upon paraffin sections through immunohistochemistry method.
Findings: The findings of the current study showed that the level of BRCA1 protein expression significantly decreased in cancerous specimens compared to healthy tissue surrounding the tumor (P = 0.026).
The expression of BRCA1 could be used as an appropriate biological marker in the diagnosis and prognosis of colorectal cancer.

The p53 tumor suppressor gene plays important roles in genomic stability. A common polymorphism at codon 72 in the p53 gene has been associated with increased risk for lung، oral، prostate، breast and colorectal cancers. Several reports have noted racial differences in the prevalence of p53 genotypes at the codon 72 in certain cancer types. We studied this polymorphism in patients with chronic myeloid leukemia in isfahan، Iran. We undertook a case-control study to examine the possible associations of the TP53 variants Arg4Pro at codon 72 with the risk of chronic myeloid leukemia. 41 whole blood specimens from healthy people as controls and 41 bone marrow specimens from patients with chronic myeloid leukemia from the city of Isfahan were analyzed. p53 codon 72 genotypes were identified using allele-specific polymerase chain reaction. The gathered data were analyzed using chi-squared test. The genotype distribution for p53 polymorphism was 43. 9%، 51. 2% and 4. 9% for the Arg/Arg، Arg/Pro and Pro/Pro genotypes، respectively in control samples; and، 31. 7%، 46. 3% and 22% for mentioned genotypes، respectively in chronic myeloid leukemia specimens. The differences in the distribution of p53 codon 72 polymorphism between the cases and controls were statistically significant (P = 0. 023). The findings of the present study indicate that p53 codon 72 polymorphism may be a genetic factor in chronic leukemia development in Isfahan. However، further studies are needed in order to elucidate the role of p53 codon72 polymorphism in chronic myeloid leukemia.

A common polymorphism at codon 72 in the p53 gene has been associated with the increased risk for lung, oral, prostate, breast and colorectal cancers. We studied this polymorphism in acute myeloid leukemia specimen from Alzahra Hospital in Isfahan city. In the present case-control study, 59 whole blood specimen from normal people and 59 acutemyeloid leukemia specimen were analyzed. p53 codon 72 genotypes were identified using allele-specificPCR. Chi-square test was used for the comparison of the frequency distribution of three genotypes of codon 72 in cases and control specimen. Resulting PCR products were either 177bp for proline allele or 141bp for arginine allele. The genotype distribution for p53 polymorphism showed 11.9%, 81.4%, and 6.8% for the Arg/Arg, Arg/Pro, and Pro/Pro genotypes in control samples and 33.9%, 61%, and 5.1% in acute myeloid leukemia specimen, respectively. The differences in the distribution of p53 codon 72 polymorphism between the cases and controls were statistically significant (p = 0.04). Deferasirox is relatively more effective than deferoxamine in reducing iron content of the liver and heart. Moreover, deferasirox is more effective in reducing cardiac iron content relative to liver iron content.

Genetic damages and epigenetic factors are important in invasive breast cancer. PTEN gene is one of the most important tumor suppressor genes. Phosphatase and tensin homolog (PTEN) protein can be traced by immunohistochemistry methods. The purpose of this study was to determine the relationship of PTEN gene expression and pathological parameters in patients with breast cancer. This descriptive analytical research was conducted on 100 cases with breast cancer admitted to a hospital in Sabzevar, Iran, during 2010-13. Samples were fixed in formalin; tissue processing and taking sections was done. Then, the slides were stained by hematoxylin and eosin. Malignancy was diagnosed by two pathologists blindly. Expression of PTEN gene was evaluated after antigen retrieval with primary specific rabbit monoclonal PTEN antibody using by immunohistochemical method. Photos were taken by light microscope. Data were analyzed using chi-square and Fisher’s exact tests. In 70 (70%) specimens, PTEN protein was detected. Protein stability was observed in total normal samples. No significant relationship was observed between the stage and grade of tumor, but there was significant relationship between PTEN gene expression and tumor grade and stage (P < 0.05). Over-expression of PTEN gene was lower in invasive ductal carcinoma compared to non-invasive breast cancers. Our study showed that PTEN gene expression is low in patients with high-grade breast tumors. Therefore, we may conclude that low expression of PTEN gene is accompanied with bad prognosis in patients with breast cancer.

Endometriosis is a female health disorder that occurs when cells from the lining of the uterus grow in other areas of the body. The cause of endometriosis is unknown. The purpose of this study was to investigate TP53 gene codon 72 polymorphism in women with endometriosis and compared it with healthy samples in Isfahan. We undertook a case-control study to examine the possible association of the TP53 gene codon 72 polymorphism with the risk of endometriosis in Isfahan. Ninety whole blood specimens from normal people as controls and ninety endometriosis specimens were analyzed. p53 codon 72 genotypes were identified using allele-specific polymerase chain reaction. Frequency of genotype Arg/Arg (Arginine/Arginine) in the samples of endometriosis was 28.9% and in healthy samples 42.2%. Frequency of genotype Pro/Pro (Proline/Proline) in the samples of endometriosis was 15.6% and in healthy ones. Frequency of heterozygote's Arg/Pro was 55.6% in endometriosis samples and 54.45% in healthy ones 3.3%. By comparing statistical genotype Pro/Pro with two other genotypes in both groups there was a statistical meaningful difference between control group and endometriosis group. [p=0.009, CI=95%, OR=5.34 (1047-19.29)]. Recent research shows that genotype Pro/Pro codon72 exon4 TP53 gene may be one predisposing genetic factor for endometriosis in Isfahan.

DAL-1 (differentially expressed in adenocarcinoma of the lung-1)، located on chromosome 18 (18p11. 3)، has been identified as a tumor suppressor gene. DAL-1 is one member of cell adhesion molecules، play role in cytoskeleton organization with intracellular tight junctions. Inactivation of this gene can destroy the intracellular and cell-cytoskeleton adhesion، which induces malignancy and metastasis. We aimed to compare the DAL-1 tumor suppressor protein expression in cancerous and normal ovarian specimens. 60 samples of ovarian cancer and 60 adjacent normal tissues from the same tumor samples were used. Immunohistochemistry method used to investigate the expression of DAL-1 protein. For scrutiny of percentage of cells in stained tissue sections، we took advantage of optical microscope and motic advanced plus 2 software. The presence of brown cytoplasm، with or without brown membrane، was considered positive for the expression of DAL-1. Significantly، expression of DAL-1 protein was reduced in tumoral tissues compared with adjacent normal tissues (P < 0. 001). Also، the decrease of protein expression was statistically related with lymph node metastasis (P = 0. 036). According to the low incidence of DAL-1 protein in tumor samples compared to normal samples in this study، DAL-1 protein expression can be related with the pathogenesis of ovarian cancer. On the other hand، significantly relation of the absence or reduce expression of this protein in cancerous samples with lymph node metastasis reveals that DAL-1 can be used as a diagnostic marker for ovarian cancer patients.

TSLC1 is a tumor suppressor protein its inactivation destroy the intracellular adhesion and connection between the membrane and cytoskeleton tend to malignant phenotype and metastasis. In this study، the expression of TSLC1 was examined in normal and cancerous ovarian cancer specimens. 60 samples of ovarian cancer and 60 adjacent normal tissues from the same tumor samples were studied. TSLC1 protein expression was evaluated by immunohistochemistry method. Percentage of cells stained from each tissue sections was checked with light microscope and Motic Advanced Plus 2 software. The presence of brown cytoplasmic membrane، with or without brown membrane، was considered positive for TSLC1 expression. Protein expression in tumor tissue was significantly reduced compared to adjacent normal tissues (P < 0. 001). The reduction of protein expression was associated with lymph node metastasis (P = 0. 028) and more advanced tumor stages (P = 0. 032). According to the reduced expression of TSLC1 protein in tumor compared to normal samples in this study، expression of TSLC1 protein may be related to ovarian cancer pathogenesis. On the other hand، reduced expression of TSLC1 protein can cause ovarian carcinoma to become aggressive. So، this protein can be used as a diagnostic molecular marker for patients with ovarian carcinoma.

P16 is known as a tumor suppressor protein. This study was conducted to evaluate the association of P16 expression and pathogenesis of colorectal cancer. The presence of P16 in cancerous and non-cancerous colorectal tissue samples were thus compared using immunohistochemistry method. In this stud, 50 paired tissue samples were provided. The pairs were comprised of samples of cancerous colorectal tissue and normal peers from non-cancerous tissue adjacent to cancerous ones. Expression of P16 was studied on paraffined sections using immunohistochemistry method. Although P16 was expressed in all tissue samples, we found a lower expression in colorectal cancerous tissue in comparison with normal tissue samples. This difference was revealed to be statistically significant (P < 0.001). The presence of P16 can be regarded as an appropriate biological marker and a valuable prognostic factor for colorectal cancer.

Colorectal cancer is one of the most prevalent gastrointestinal malignancies. Expression of some proteins including P53, P21, E-cadherin and β-catenin is assumed to have a prognostic role for this malignancy. In the present study we evaluated the association of retinoblastoma (RB) protein expression and pathogenesis of colorectal cancer. The presence of RB in cancerous and non-cancerous colorectal tissue samples were compared using immunohistochemistry method. Tissue sections were taken from tumoral and non-tumoral defined areas of 50 colorectal cancer patients. After coloration according to immunohistochemistry method, all samples were studied for RB expression. We found RB expression in colorectal tumoral cells to be significantly higher than that of non-tumoral cells (P < 0.0001). RB overexpression in cancerous cells may lead to insensibility to apoptosis and consequent long life of affected cells as well as resistance to treatment.

The tumor suppressor in lung cancer-1 (TSLC1) is a tumor-suppressor gene. We evaluated the correlation between TSLC1 expression and clinicopathological characteristics of colorectal cancer patients by comparing primary colorectal cancer and adjacent normal colorectal tissues. TSLC1 expression was evaluated in 100 pairs of primary colorectal cancerous and corresponding normal colorectal tissues using immunohistochemical staining on paraffin-embedded sections. The correlation between immunohistochemical findings and clinicopathological factors was then investigated. Age, gender, and clinicopathological presentation of patients were also noted. TSLC1 was expressed in all tissues. A 71%- down regulation of TSLC1 was colorectal cancer specimens compared to the matched normal tissues. There were statistically significant correlations between TSLC1 expression and stage, location, and lymph node metastasis. TSLC1 expression may be a favorable biologic marker and a useful prognostic indicator in patients with colorectal cancer.

Prostate cancer is an important disease whose many genetic aspects are still uncovered in spite of the wide spectrum of the studies previously performed on its genetic and environmental risk factors. According to the previous studies, KLF6, a suppressor gene dealing with prostate cancer, is exposed to genetic changes. Among all these changes, mutation of exon No. 2, which is in relation with disease prognosis, is common. The few studies conducted on the mutation of KLF6 gene have shown a relation between mutation and environmental factors as well as race and geographic conditions. The goal of this study was to investigate the mutation of exon No. 2 of KLF6 gene in people who suffer from prostate cancer in city of Isfahan, Iran. The study was carried out on microscopically and pathologically proved cases of prostate cancer in Isfahan, Iran, during 2009-2011. The samples were taken by prostatectomy or biopsy from 40 patients suffering the disease. A procedure including DNA extraction, determination of quality and quantity of DNA, PCR (using specific primers to replicate exon No. 2), polyacrylamide gel electrophoreses, and data analysis was performed on the samples to determine the mutation in exon No. 2 of KLF6 gene. Overall, 80% of the patients (32 people) were above 60 years of age. Only 17.5% of the patients (7 people) had mutation in exon No. 2 of KLF6 gene. There was no significant relation between the mutation of exon No. 2 of KLF6 gene and the age of the patients. A significant relation was found between the presence of mutation and tumor grading in the studied patients. The frequency of mutation in exon No. 2 of KLF6 gene was higher in cancer samples with higher grade. This finding can be a sign of weak prognosis in samples whose exon No. 2 of KLF6 gene has been mutated.

APC is a tumor-suppressor protein. To evaluate the correlation between APC expression and pathogenesis of colorectal cancer, we investigated the expression of this protein in cancerous and normal colorectal tissues. APC expression was evaluated in 50 pairs of primary colorectal cancers and corresponding normal colorectal tissues using immunohistochemical staining on paraffin-embedded sections. APC was expressed in all tissues. It was down-regulated in the colorectal cancer specimens compared with the matched normal tissues (P < 0.001). APC expression may be a favorable biologic marker and a useful prognostic indicator in patients with colorectal cancer.

Endometriosis is a common disease among women which is a result of endometrial tissue growth outside the uterus. However, its cause is still unclear. This study surveyed TP53 codon 72 gene polymorphism among 90 patients suffering from endometriosis and 90 healthy subjects, as the control group, in Isfahan. Different genotypes of TP53 codon 72 gene were determined by polymerase chain reaction (PCR). The frequency of Arg/Arg (Arginine/Arginine) genotype in subjects with endometriosis and healthy individuals were 28.9% and 42.2%, respectively. In addition, the frequency of Pro/Pro (Proline/Proline) genotype in patients with endometriosis and healthy participants were 15.6% and 3.3%, respectively. The frequency of heterozygotes Arg/Pro was 55.6% in endometriosis patients and 54.45% in healthy subjects. Comparing the frequency of Pro/Pro genotype with the two other genotypes in both groups revealed a statistically significant difference between the control and endometriosis groups [P < 0.05; CI = 95%; OR = 5.34 (range: 1047-19.29)]. The present research showed that Pro/Pro genotype of TP53 codon 72 gene is a predisposing genetic factor for endometriosis occurrence in Isfahan.

The P53 tumor suppressor gene plays important roles in genomic stability. G–to-C at codon 72 in the P53 gene has been associated with increased risk for lung, oral, prostate, breast, colorectal cancers and may be a marker for risk of skin cancer. This project studied the effect of P53 polymorphism on risk of nonmelanoma skin cancers (Squamous and basal cell carcinoma). This case–control study undertook for study of twenty basal cell carcinoma (BCC), twenty squamous cell carcinoma (SCC) and twenty specimens as controls for each cancer specimen in the city of Isfahan, Iran. Different P53 codon 72 genotypes were identified using polymerase chain reaction. In control samples, the frequency of Arg/Arg genotype showed 25% and in BCC specimens showed 60%. The differences in this genotype group between the cases and controls were statistically significant (P = 0.048). The differences in the frequency of heterozygot Arg/Pro and also in the frequency of Pro/Pro genotype between the cases and controls were not statistically significant. OR = 4.5 in BCC cases show that the risk for this disease in persons who have Arg/Arg genotype is about 4.5 times more than normal people. The results of χ2 test showed that in this study there is not statistically significant differences between the SCC specimens and controls for frequency of different genotypes. The present study indicate that P53 codon 72 polymorphism is a genetic predisposing factor for risk of nonmelanoma skin cancers (of BCC type) in Isfahan. However, further studies are needed in order to elucidate the role of P53 codon 72 polymorphism in skin cancer development.

The polymorphic variants at codon 72 of the p53 gene, encoding proline or arginine at residue 72, produce marked changes in the p53 structure. From the evidence that the DNA mismatch repair system and p53 interact to maintain genomic integrity, we hypothesized that codon 72 variations may influence the prevalence of microsatellite instability (MSI), a feature of malignancies associated with mismatch repair deficiency in sporadic colorectal cancer. We investigated the frequency of MSI in three P53 codon 72 genotypes using genomic DNAs from 144 paraffin blocks of sporadic colorectal adenocarcinomas by testing the BAT-26 poly(A) marker. We used PCR-SSCP analysis to detect tumor sample MSI for the nonisotopic detection of deletions in the BAT- 26 poly (A) mononucleotide repeat. Associations between qualitative variables were evaluated using the χ2-test. Statistical significance level was set to p ≤ 0.05. MSI analysis revealed that 24.3% of the tumors (n=35) were MSI-positive and 75.7% (n=109) were MSI-negative. The frequency of microsatellite instability in the arginine/arginine, arginine/proline and proline/proline genotypes were 11 (16.9%), 22 (36.1%) and 2 (11.1%) respectively. A significant difference in distribution of MSI was found for the arginine/proline genotype compared with the grouped arginine/arginine and proline/proline genotypes (p=0.05). Our findings suggested that colorectal adenocarcinomas arising in individuals with the p53 codon 72 arginine/proline heterozygosity are more prone to microsatellite instability than those with other p53 genotypes. In our study, MSI was important in the carcinogenesis of sporadic colorectal cancer arising in pro/arg heterozygotes.

A single nucleotide polymorphism at codon 72 of the p53 gene alters the p53 protein structure and affects its activity. This polymorphism depends on geographic regions and race. Also its association with some cancers has been reported. The aim of this study was to investigate this polymorphism in well differentiated oral SCC and normal population in the city of Isfahan. In this case-control study, 20 paraffin blocks of non metastatic and well differentiated oral SCC were selected from the archive of oral pathology department of dental school between 2001 and 2005. 20 whole blood samples from normal people were considered as control group. After DNA extraction, p53 codon 72 polymorphism was determined by polymerase chain reaction (PCR) technique using specific primers of Arg and Pro and agarose gel electrophoresis. Data were analyzed by Fisher's exact test with p<0.05 as the level of significance. The prevalence of Arg/Arg, Arg/Pro and Pro/Pro genotypes in case group were 45%,45% and 10% respectively compared to 45%,50% and 5% in controls. There was no statistical significant difference in p53 codon 72 genotypes distribution between case and control groups. Based on the results of this study, p53 polymorphism could not be considered as a genetic predisposing factor for oral SCC development in Isfahan.

The p53 tumor suppressor gene plays an important role in genomic stability. A common G-to-C polymorphism at codon 72 in the p53 gene has been accompanied with high risk of lung, nasopharyngeal, oral, prostate, and colorectal cancers, and may result in genetic susceptibility to breast cancer. We studied the effect of this p53 polymorphism on breast invasive ductal carcinoma development This case–control study was conducted among 51 patients with breast invasive ductal carcinoma and 51 matched controls in Isfahan. P53 codon 72 genotypes were identified using allele-specific polymerase-chain reaction (PCR). In control samples, the genotype distribution of p53 polymorphism showed 43.2%, 52.9% and 3.9% for the Arg/Arg, Arg/Pro and Pro/Pro genotypes, respectively. In cancer group the distribution was 86.2% for Arg/Arg, 11.8% for Arg/Pro and 2% for Pro/Pro. Distribution differences in p53 codon 72 polymorphism between the cases and controls were statistically significant (P)