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KMID : 0948320050050010064
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Konyang Medical Journal
2005 Volume.5 No. 1 p.64 ~ p.76
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Mutation of K-Ras, APC Genes and Expression of Mutant P53 Protein Associated with Colorectal Adenoma and Adenocarcinoma
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Min Seong-Ki
Kim Yoon-Mee
Lee Jung-Uee
Mok Woo-Kyun
Suh Kwang-Sun
Kim Bum-Kyeong
Sul Hae-Joung
Kim Hoon
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Abstract
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The purpose of this study is to assess the roles of oncogene, K-Ras and tumor suppressor gene, APC(adenomatous polyposis coli) and mutant p53 protein associated with development of colorectal carcinoma based on the adenoma-carcinoma chain introduced by Vogelstein et al. I used the permanently paraffin-embedded tissue, 38 adenomas removed by colorectal endoscopy and 49 adenocarcinomas radically or widey excised between on Febraury in 2000 and on July in 2001 in Konyang University Hospital. I reviewed the microscopic slides with clinicopathological reports and performed immunohistochemical staining for p53 with all specimens. Also, I performed PCR-SSCP for detection of K-Ras and APC gene mutation with all specimens after DNA extraction from the paraffin-embedded tissue. Results are following: 1. In 38 cases of adenoma having 15 mutation (39.5%) for K-Ras and 6 mutation (15.8%) for APC, there were no statistical correlations beween mutational status for K-Ras, APC and clinicopathological factors including tumor size, growth pattern, but the adenomas showing villous pattern showed increased mutational frequencies for K-Ras (tubular: 37%, villous: 45.4%) and APC (tubular: 14.8%, villous: 18.3%). 2. In 49 cases of adenocarcinoma having 16 mutation (32.7%) for K-Ras and 12 mutation (24.5%) for APC, there were no statistical correlations between mutational status for K-Ras, APC and clinicopathological factors, such as size, differentiation, stage and lymph node metastasis. 3. In 49 cases of adenocarcinoma showing fungating growth in 16 cases (32.7%) and infiltrating growth in 33 cases (67.3%), the differentiation pattern was statistically correlated with growth patterns of the adenocarcinoma (P value: 0.03). The larger the size was, the more frequent the growth pattern was infiltrating. And the fungating adenocarcinomas were more frequently developed in the right side of the colon, but these were statistically insignificant. 4. In immunohistochemical staining of adenocarcinomas for mutant p53 protein, 26 cases (53.1%) were expressed. There were statistically significant correlations with tumor size(P value:0.04, <3.5:1 of 6 cases (16.7%), 3.5-4.9:10 of 17 cases (47.1%), =5:15 of 26 cases (57.7%)), stage (P value:0.03, 7 (33.3%) of 21 B1+B2 cases, 15 (65.2%) of 23 C1+C2 cases, 4 (80.0%) of 5 D cases), and lymph node metastasis status (P value:0.04, +:19 (64.3%) of 28 cases, -:7 (33.3%) of 21 cases). However, there was no statistical correlation between p53 expression and differentiation. 5. In the aspect that adenoma and adenocarcinoma are developing along the continuous spectrum in cancer development, the expression of p53 was statistically correlated with the size (P value:=0.04, 3 cases (13.0%) of 23 adenomas less than 1, 3 cases(20.0%) of 15 adenomas larger than 1, and 26 cases (53.1%) of 49 adenocarcinomas) and stage (P value:=0.01, 6 cases (15.8%) of 38 cases of adenomas, 7 cases (33.3) of 21 B1+B2 stage, 15 cases (65.2%) of 23 C1+C2 stage, and 4 cases (80.0%) of 5 D stage in 49 cases of adenocarcinoma). The above results suggested that mutation of K-Ras and APC genes are contributing to the development of colorectal carcinoma in early stage of the process, but mutation or loss of p53 gene with production of mutant protein or not is eventual step to the true neoplasm acquiring malignant biologic behavior.
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KEYWORD
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Adenoma, Adenocarcinoma.K-ras, p53, APC
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