ABSTRACT
Reports of cases of flat-type colorectal tumors are increasing in Japan, but almost nothing has been elucidated about the genetic abnormalities of these tumors. In this study, we have examined p53 mutations in six cases of colon cancer cell lines, 22 cases of flat-type colorectal tumors, and 27 cases of polypoid-type colorectal tumors using the polymerase chain reaction (PCR) and temperature-gradient gel electrophoresis (TGGE); the latter has recently been developed as a screening method for gene mutations. p53 mutations were observed in four colon cancer cell lines, six flat-type colorectal tumors, and three polypoid-type colorectal tumors, all of which were analyzed by direct sequencing. These mutations were observed only in adenomas with high-grade dysplasia and in colorectal cancers but not in adenomas with low-grade dysplasia. These observations suggest that p53 gene mutations are involved in flat-type as well as polypoid-type colorectal tumors at relatively later stages of carcinogenesis and that TGGE seems to be useful as one of the rapid screening methods.
Subject(s)
Colorectal Neoplasms/genetics , DNA Mutational Analysis/methods , Electrophoresis/methods , Genes, p53/genetics , Point Mutation , Adenoma/genetics , Adenoma/pathology , Base Sequence , Colorectal Neoplasms/pathology , DNA, Neoplasm/analysis , DNA, Neoplasm/genetics , Humans , Molecular Sequence Data , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , Polymerase Chain Reaction , Tumor Cells, CulturedABSTRACT
Ras gene mutations occur relatively early during colorectal tumor development and have been observed in 40-50% of malignant colorectal tumors. Advances in endoscopic techniques have made it possible to detect small, flat colorectal tumors that could not be detected by standard examinations. To determine whether ras gene mutations are also involved in the genesis of small, flat colorectal tumors, we examined ras point mutations in 34 cases of small polypoid or flat elevated colorectal tumors (32 adenomas, 2 carcinomas) and in 26 cases of small, flat colorectal tumors (13 adenomas, 13 carcinomas) by means of the polymerase chain reaction (PCR) and dot-blot hybridization. Ras gene point mutations were observed in 16 of the 34 tumors of the former type (47%), but in none of the 26 tumors of the latter type, even though the grade of dysplasia was severe in the flat tumors. Our results suggest that different genetic pathways for tumor progression may exist for polypoid and for flat colorectal carcinomas.
Subject(s)
Adenoma/genetics , Colorectal Neoplasms/genetics , Genes, ras/genetics , Point Mutation/genetics , Adenoma/pathology , Base Sequence , Colorectal Neoplasms/pathology , Humans , Immunoblotting , Nucleic Acid HybridizationABSTRACT
BACKGROUND: Parathyroid hormone-related protein (PTHrP) has been regarded as one of the substances causing humoral hypercalcemia of malignancy. METHODS: The immunohistochemical localization of PTHrP was investigated in 33 cases of gastric cancer (4 with heterotopic ossification and 29 without heterotopic ossification) to clarify the role of PTHrP in heterotopic ossification by using the anti-PTHrP monoclonal antibody, 4B3. RESULTS: The four cases with heterotopic ossification showed positive staining at primary or metastatic sites, and in one case fibroblasts in the stroma surrounding the heterotopic ossifying foci also showed positive. On the other hand, of the 29 cases without heterotopic ossification, only 5 showed positive staining. CONCLUSIONS: The presence of PTHrP in ossifying gastric carcinomas at a relatively high rate indicates that PTHrP also might be related to heterotopic ossification associated with malignancies. It is speculated that PTHrP would contribute to heterotopic ossification by facilitating the process of mineralization.
