الفهرس 
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Abstract
Pancreatic carcinoma is one of the most lethal solid tumors; which represents the 9th most frequent malignancy and the 3rd leading cause of cancer death in the United States. Patients with pancreatic carcinoma have a dismal prognosis; if not take any measures to treat patients with the disease, the median 5-year survival is only about 4%. In Egypt, the disease has traditionally been considered rare, but population in the East Nile Delta region of Egypt exhibits an unusually high rate of young-onset pancreatic cancer. Local invasion and distant metastasis are the important biological characters of pancreatic carcinoma.
Matrix metalloproteinase; MMP-2 is a member of MMPs family which is zinc-dependent endopeptidases that degrade all components of ECM and vascular basement membrane. They play an important part in the development of numerous neoplasms. MMPs are closely involved in tumor invasion and metastasis.
Survivin plays an important role in regulation of apoptosis. Survivin is unique for its expression in human malignancies but not in normal adult cells. Survivin expression is associated with metastasis, local recurrent disease and poor prognosis.
In the current study, we evaluate the IHC expression of MMP-2 and Survivin in pancreatic carcinoma and its correlation with the established prognostic factors such as tumor size, histological type, tumor grade of differentiation, perineural invasion, lymphovascular invasion, lymph node metastasis and tumor stage.
The current study was carried out on 30 formalin-fixed paraffin-embedded tissue blocks; 25 cases of pancreatic carcinoma and 5 cases of chronic pancreatitis as a control. The mean age of the patients was 56.32 years ranging from 40 to 69 years. Males were more frequently involved by pancreatic carcinoma than females.
Histopathological examination showed that 24 specimens were PDAC; 5/25 cases of well differentiated, 16/25 cases of moderately differentiated and 3/25 cases of poorly differentiated pancreatic carcinoma and one specimen was acinar cell carcinoma. Perineural invasion was observed in 20/25, while vascular invasion was observed only in 2/25 of the studied tumors. Lymph node involvement was observed in 13/25 of the tumors. Regarding tumor stage, most cases of this study were classified as either pT2; 12/25 cases or pT3; 6/25 cases.
MMP-2expression:
MMP-2 expression was cytoplasmic in pancreatic carcinoma cells and its expression level is generally high as the IRS was ranged from 6/9 to 9/9 with high extent and intensity. This expression was detected in 22/25 (88%) of the studied pancreatic carcinoma specimens. Stromal cells showed positive staining in 12/25(48%) of pancreatic carcinoma specimens in the current study. Non-neoplastic acinar parenchymal, pancreatic ductal epithelium and chronic pancreatitis specimens were negative for MMP-2.
In this study, there was a significant correlation between MMP-2 expression in pancreatic carcinoma cases and poor histological grade. There was no statistically significant correlation between MMP-2 expression and other studied clinico-pathological parameters of pancreatic carcinoma; tumor size, perineural or lympho-vascular invasion, lymph node metastasis, or tumor stage.
Survivin expression:
In this study, Survivin expression was cytoplasmic and its level is generally high as the IRS was ranged from 9/12 to 12/12 with high extent and intensity. This expression was detected in 23/25 (92 %) of pancreatic carcinoma. Non-neoplastic acinar parenchymal, pancreatic ductal epithelium and chronic pancreatitis specimens were negative for Survivin with positive staining of endocrine cells of Islets of Langerhans.
In this study, there was a significant correlation between Survivin expression in pancreatic carcinoma cases and poor histological grade. There was no statistically significant correlation between Survivin expression and any of the studied clinico-pathological parameters of pancreatic carcinoma; tumor size, perineural or lympho-vascular invasion, lymph node metastasis, or tumor stage.
There was a statistically significant positive correlation between Survivin expression and MMP-2 expression in pancreatic carcinoma.
Conclusion
In conclusion, taken together, our findings on the two studied biomarkers we can say that:
• MMP-2 and Survivin immune expression was positive in pancreatic carcinoma with various grades, but negative in non-neoplastic acinar parenchymal and pancreatic ductal epithelium and in chronic pancreatitis patients.
• There was a significant relationship between MMP-2 and Survivin expression and poor histological grade in PDAC.
• Although MMP-2 and Survivin immune expressions were increased in large sized pancreatic carcinomas, perineural invasion and advanced tumor stages (T3/T4), there was no significant correlation between MMP-2 and/or Survivin expression and most of the studied clinico-pathological parameters.
• There was significantly positive correlation between Survivin and MMP-2 expression in pancreatic carcinoma.
Recommendations
All these preliminary data require more in-depth studies such as, performance on a large number of cases with different pancreatic carcinoma types, grades and stages to improve the statistical power and reduce statistical bias, and to establish the correlations between MMP-2 and Survivin expressions and different clinic-pathological parameters.