الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Breast cancer is the most common cancer and the second most common cause of cancer death in women in the U.S. Heightened awareness of breast cancer risk in the past decades has led to an increase in the number of women undergoing mammography for screening, leading to detection of cancers in earlier stages and a resultant improvement in survival rates. Still, breast cancer is the most common cause of death in women between 45-55 years of age.
The p53 gene is located on chromosome 17 and acts to regulate the cell cycle. It is rather unreactive in cells where DNA is undamaged. When there is DNA damage, however, the p53 gene suspends the cell cycle until the damage can be repaired. If there is a mutation in p53, the cell cycle continues unrestrained and reproduces the damaged DNA, leading to uncontrolled cell proliferation and cancer. Nearly half of all human cancers are related to a mutation in the gene, making it the most frequently encountered mutation in all of cancer. Among the carcinogens that affect p53 are ultraviolet radiation and cigarette smoke. Accumulation of mutant p53 in tumor cells can lead to the production of p53 antibodies in serum. Such antibodies correlate closely with other factors that indicate poor prognosis. These findings suggested to evaluate p53 antibody in breast cancer patients undergoing surgery for locoregional disease and the relation between this antibody and histopathological or clinical indices.
Survivin has recently been identified as a novel inhibitor of apoptosis (IAP). Unlike other members of the IAP family, survivin is characterized by a unique structure that contains a single baculovirus IAP repeat and no really interesting new gene (RING) finger motifs, and it is expressed in many common human cancers, but not in normal tissues. Survivin regulates the G2/M phase of the cell cycle and it directly inhibits caspase-3 and caspase-7 activity. During tumorigenesis, survivin expression is inversely correlated with apoptosis inhibition and positively correlated with proliferation and angiogenesis. Inhibition of apoptosis by survivin predicts poor prognosis and shorter survival in human cancers.
The study aims to elucidate the relationship between survivin and p53 in breast cancer patients and to correlate them with various clinicopathological parameters associated with the disease and to assess the diagnostic significance of survivin and p53 in breast cancer patients.
The study included 40 subjects divided into 2 groups: GroupI which included 25 females recently diagnosed with breast cancer and GroupII which included 15 normal healthy females as a control group.
Patients were selected from those admitted to the Experimental and Clinical Surgery Department and Cancer management and Research Department, Medical Research Institute, Alexandria University.
A blood sample was collected from each patient of Group I before surgery, after surgery and after 6 cycles of chemotherapy. from Group II subjects, a single blood sample was collected. Serum was immediately separated from all collected samples. All sera was kept frozen at -80C until used. p53, survivin and CA15.3 were assayed by commercially available ELISA kits in all serum samples collected.
P53 and survivin are usually evaluated by immunohistochemistry in tumor tissue specimens, but this technique requires a high quality tissue sample which may not be available and is also observer dependent. An ELISA assay has been developed for measuring circulating concentrations of each of them. Some of the advantages of ELISA as a method are that it is reproducible, quantitative and objective, and that blood collection is much less invasive than tissue sampling and is collected routinely before administration of chemotherapy.
In the current study, p53 level in cancer patients before surgery was statistically significantly higher than in control subjects (24.26 vs 2.62 U/ml, respectively, p < 0.001). P53 levels remained significantly higher than controls after surgery and after chemotherapy, but not significantly different from each other or from before surgery (22.47 and 21.45 respectively).
Survivin levels measured in the study showed a different pattern from that of p53. Survivin level in cancer patients at presentation before surgery was statistically significantly higher than in control subjects (66.96 vs 25.95 pg/ml, respectively, p = 0.002). Survivin levels significantly decreased after surgery and after chemotherapy to become similar to control level (27.27 and 24.85 respectively), and significantly higher than before surgery.
Upon evaluation of the ROC curves of the three markers, both p53 and survivin were significant (p = 0.001and 0.001) but not CA 15.3 (p = 0.058), with AUCs; 0.9 for p53, 0.89 for survivin and 0.72 for CA 15.3.
These results suggest that serum p53 is the best candidate for a diagnostic marker of breast cancer. At an optimum cutoff value of 1.1 U/ml, p53 had a sensitivity of 96.0%, specificity of 77.8% and accuracy of 91.2%. While survivin is also a good candidate for a diagnostic marker of breast cancer. At an optimum cutoff value of 18 pg/ml, survivin had a sensitivity of 96.0%, specificity of 60.0% and accuracy of 85.7%.While the non-significant CA 15.3, at an optimum cutoff of 1.1 U/ml, it had a 100% sensitivity, a very low specificity of 40% and an accuracy of 82.9%.
In conclusion, serum p53 and survivin measured by EISA are probably good diagnostic markers for primary breast cancer. Their ROC curve analysis revealed that they are better diagnostic markers than CA 15.3, which currently is the gold standard for breast cancer diagnosis. The fact that they are not significantly correlated to any of the clinicopathological parameters of the disease may be due to the small sample size of the cohort under investigation. This work needs to be further expanded and re-evaluated on a much larger population of patients and with follow up for these results to be conclusive.