الفهرس 
Genes and cancerOnly 14 pages are availabe for public view
 |  | from | 16 |  |  |
| | | from | 16 | | |
Abstract
Since long time the prognostic significance of tumor stage, grade and lymph node involvement have been emphasized. Patients with identical or similar features (grade, stage, lymph node status, etc.) are categorized into certain prognostic groups. the members of which ,are expected to follow similar clinical course. Unfortunately, tumors belonging to one prognostic group demonstrated a wide range of outcomes and behavior making it difficult to establish a prognosis and an appropriately individualized plan of treatment. With these general considerations in mind, this work aimed at exploring the potentialities of utilizing p53 overexpression as a prognostic parameter in cases of colorectal carcinoma. This was planned to be achieved through: a) Study of the prevalence of p53 overexpression in colorectal carcinoma and other benign colorectal lesions by immunohistochemical method. b) Study of the correlation between p53 overexpression and other histopathological parameters of established prognostic significance. c) Study the relation of p53 overexpression, and other histopathological parameters with survival. The material of this work consisted of 85 colorectal tissue specimens including 40 cases of colorectal carcinoma, 15 cases of C.R. adenomatous polypi, 15 cases of ulcerative colitis and 15 cases of C.R. Bilharziasis. Ten cases have been taken as negative control from healthy colonic mucosa. Two 5-micron thick sections were obtained from each specimen prepared for staining by p53 monoclonal antibodies and Haematoxylin & Eosin. For each case data about age, sex, size and site of the lesion, histopathologic type, pathologic stage and lymph node status were obtained. Cases we’re followed up till the end of June 1997. The follow up period for patients with C.R. carcinoma ranged from 19 - 36 months with a mean period of 25.11 months. The results of immunostaining for p53 overexpression were divided into two main groups: the negatively stained, where there was no evidence of nuclear staining and the positively stained cases. Positive cases were categorized into 3 groups by counting the number of positive cells in at least five representative microscopic high power fields: (1) Mild or (+) when up to 250/0 of cells stain positive, (2) Moderate (++) when more than 25% up to 50% of cells stain positive, and (3) Marked or (+++) for cases showing more than 50% positive cells. The mean age for patients with colorectal carcinoma was 44.2 years, for ulcerative colitis was 35.1 years, for C.R. Bilharziasis was 29.3 years and for C.R. adenomatous polypi was 16.2 years. The male/female ratio in our cases was 1.4. In twenty five cases (62.50/0) out of the 40 cases of colorectal carcinoma the lesions were located in the rectosegmoid region and 15 cases (37.5%) were located in the entire colon. 30 cases (750/0) out of the 40 cases of colorectal carcinoma were in the stage of Dukes C and 10 cases (25%) were in the stage of Dukes B. This means that 75% of the patients of colorectal carcinoma came late to the National Cancer Institute and Menoufiya University Hospital. 70% of the tumors ’were of grade 2 and 30% were of grade 3. Lymph node metastases were present in 750/0 of the cases of colorectal carCInoma.’ None of the normal control cases stained positive for p53. , p53 overexpressionwas observed in 72.50/0 of the cases of colorectal carcinoma, denoting involvement of p53 mutations in the molecular pathogenesis of colorectal carcinoma. p53 expression of the mild type was also observed In one case (6.7%) out of the 15 cases of ulcerative colitis , In this case there was marked dysplastic changes in the crypts. In this case of ulcerative colitis in which there was positive p53 expression malignant transformation potential must be predicted. Neither the 15 cases of colorectal adenomatous polypi nor the 15 cases of colorectal Bilharziasis showed any nuclear p53 overexpression. This finding was supported by the fact thatI, p53 overexpression was restricted to cancer cases and glands with dysplastic, changes and not in normal mucosa or inflammatory lesions. p53 overexpression was found to be correlated with the stage and grade of the tumors and with lymph node metastases and was found to be not correlated with age, sex, tumor size and .histologic type of the tumor. The observed 36 months survival rate was 45.9%. p53 overexpression was found to be correlated significantly with survival. The 36 months disease free survival rate for p53 negative cases was 900/0 in marked contrast to 29.60/0 for the p53 positive cases. Intensity of positive staining also correlated significantly with survival. Multiple regression analysis had shown that p53 overexpression is th~ most independent factor in its relation to survival. In this study sui~ival was observed to decrease as tumor grade increased. Observed survival was 600 /0 for grade 2 tumors and 16.70/0 for grade 3 tumors. Survival was also observed to decrease as the stage of the disease increased. Survival was 66.7% for patients in Dukes Band 39.3% for those in Dukes C. No significant correlation had been observed between survival and age, sex, size of the tumor and histologic type of the tumor.