Tumorigenesis from the benign and precancerous lesion has long been thought to be a multistep process. Among them, point mutation of ras oncogene was studied in several investigations as an initial event of tumorigenesis of human colorectal
cancer.
Ras oncogene encoded protein product p21 has been known to regulate cell proliferation and differentiation by p21 GTP(guanosine 5'-triphosphate) or GDP(guanosine diphosphate) complex with point mutation. Activation of cellular ras genes is caused
by
single base mutation resulting in an amino acid substitution yielding p21 species with increased transforming ability. Immunohistochemical and molecular cytogenetic studies of colon and rectal neoplasms indicated that in 40~50% of cases mutated
ras
oncogenes can be identified. But, the function of p21 has not been known precisely, yet.
We undertook the immunohistochemical study of the ras p21 protein product in a series of normal colorectal tissues, benign tumors, colorectal cancers and metastatic lymph node tissues with K-ras and H-ras monoclonal antibody. Benign tumors were
divided
into three groups by dysplasia, size and pattern of nuclear arrangement and mucinous component in cytoplasm. Malignant tumors were classified into 4 groups by Astler Coller's modification of Dukes' classification. The purpose of this study was to
find
out the importance and clinical application of malignant teansformation of benign tumors by detection of expression of p21 encoded by K-ras or H-ras oncogene.
@ES The results were obtained as follows:
@EN 1) The expression of the p21 of K-ras oncogene in normal tissues, benign tumors, malignant tumors and metastatic lymph nodes were 13.3%, 34.8%, 40.2% and 20.0%, respectively. And expression of the p21 of H-ras were 13.3%, 50.7%, 16.7% and
35.0%,
respectively.
2) The expression of the p21 of K-ras and H-ras in benign tumor was divided into 3 groups. And the rate of the group 1 showed lowest rate as 11.1% and 27.8%. The expression rate was increased to 40.0% and 80.0% in group 2, 61.5% and 69.2% in
group
3.
3) The expression of the p21 in colorectal cancer was slightly different in various stages using the K-ras monoclonal antibody 50%, 50%, 33.3% and 36%, respectively. But, the results of Hras p21 was varied 58.3%, 70%, 70% and 64%, respectively.
4) In according to the differentiation of the colorectal cancer, the expression of the p21 K-ras was 44.4% in well differentiation group, 34.2% in moderate group, 46.1% in poorly group. In the case of p21 of H-ras, 75.0% in well differentiated
group,
63.2% in moderate differentiated group and 53.9% in poorly differentiated group were evaluated.
5) In a point of intensity of staining, the proportion of strong stained specimen was slightly different in each group, but there was no significant discrimination statistically.
With above results, authors considered that ras oncogene encoded protein product p21 plays an important role in colon and rectal carcinogenesis at the early stage, especially in the progression of adenoma, and may be useful in early detection and
prediction of progression of colorectal cancer.
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