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Abstract Summary & Conclusion ”” SUMMARY AND CONCLUSION Summary: In Egypt, colorectal cancer is the seventh most common cancer according to Cancer Pathology Registry (Soliman et aL, 1997). In United States, colorectal carcinoma is the second most common malignancy after lung cancer, comprising 10-15% of all malignancies. It shows wide variation in incidence throughout the world (Potter, 1997). The present study aims at evaluation of the proliferative activity of different histopathologic colorectal tumors among Egyptians. Tumor were classified according to WHO classification, using two different methods of cellular proliferation; the monoclonal antibody PCNA LI and silver-stained nucleolar organizer regions. The second aim was to correlate their results with other clinicopathologic variables including age, sex, site, metastases, grade, stage, and depth of invasion, recurrence and survival. Statistical analysis and correlations were made for all these variables. Our material of study included 46 cases of colorectal tumors which were diagnosed and treated at the Faculty of Medicine Benha University and the Armed Forces hospital during the period between July 1990 and January 1995. All of the patients underwent resection of the tumor combined with lymph node dissection and none of them received preoperative chemotherapy or radiotherapy. Additional 6 normal colonic specimens were taken as a control. 166 Summary & Conclusion ~ The PCNA Labeling Index (PCNA-LI) was determined as the percentage of positive cell nuclei. Cases were then classified into high and low PCNA LI according whether the value was above or below the median PCNA LI. Also AgNOR score was divided into low and high according to the mean. Morphology and distribution of AgNOR was taken into consideration. Statistical analysis was performed by the student ”t” test, the chi square test and the Fisher exact probability calculation method. The correlation between PCNA LI and AgNOR score was studied using linear regression. The outcome of different groups of patients was compared by the generalized Wilcescan test. Statistical significance was defined as P<0.05. The histopathologic findings showed that out of 46 cases studied, 4 cases adenoma, 42 cases colorectal cancer; including 8 WDA, 12 MDA, 7 PDA, 9 MUC and 6 SRC. Also, we added 6 cases as a control. Lymph node, liver and peritoneal metastases were detected in 21, 13 and 7 cases respectively. Out of the 42 colorectal cancer, 23 had recurrence and 22 died. Eleven cases were stage Bl, 9 stage B2, 5 stage Cl, 11 stage C2 and 4 cases stage D. The immunohistochemical results of PCNA LI varied between different colorectal groups, where it increased gradually with progression and proliferation of the lesions from apparently normal mucosa (1.33 + 1.2) to adenoma (20.25 ± 3.3) to colorectal cancer (46.9 ± 23.44), where 167 Summary & Conclusion ’” P<O.00 1. PCNA LI was found to correlate well with tumor stage, depth of invasion, metastases and survival. The prognosis of high PCNA group was significantly worse than that oflow PCNA group, P<O.OOl based on survival and metastases. The AgNOR counts were found to correlate significantly and increase gradually with progression of colorectal lesions. The mean numbers of AgNORs dots/nucleus was evaluated in apparently normal mucosa (1.97 + 0.51), in adenoma (3.28 + 0.8) and in colorectal cancer (5.6 + 1.95), where P<O.OO1.An overlap was found between individual cases of the malignant groups. The AgNOR score was found to correlate well with tumor stage, depth of invasion, metastases and recurrence. The prognosis of high AgNOR group was significantly worse than that of the low AgNOR group, P<O.OOl. As regards the AgNOR morphology and distribution pattern, it was found to show a characteristic difference between benign and malignant groups of colorectal tumors. Malignant cells were characterized by an irregularly scattered distribution ofNORs and by a pleomorphic size and shape of the dots in comparison to the rounded, uniform and regular size and shape with regular dispersion in the nucleoplasm of the NORs dots in benign lesions. from the combined analysis of AgNOR score and PCNA LI, we found that the high AgNOR, high PCNA group had the poorest prognosis, on the other hand low AgNOR, low PCNA group had the best. We suggest that nucleolar organizer regions were the most reliable 168 Summary & Conclusion l<1 prognostic variable for predicting recurrence irrespective to PCNA. While PCNA could be more accurate in predicting survival. These results indicate that simultaneous determination of AgNOR score and PCNA LI is more serviceable than either alone for the precise evaluation of prognosis for colorectal carcinoma patients. |