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.

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.

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.

We report a case of a huge polypoid-type early gastric neuroendocrine cell carcinoma. Upper gastrointestinal endoscopy in a 77-year-old man revealed a gastric polyp on the anterior wall of the corpus. Endoscopically biopsied material from the polyp suggested that the lesion was malignant; specifically a poorly and moderately differentiated tubular adenocarcinoma or adenocarcihoma with neuroendocrine differentiation. Endoscopically the lesion was a huge polypoid type with a broad stalk approximately 40 mm in diameter, and its surface was lobulated with a white coat and erosion. The patient underwent total gastrectomy. The resected specimen histopathologically showed a polypoid mass with medullary carcinoma and indicated endocrine cell differentiation. Immunohistochemical findings supported the diagnosis of endocrine cell carcinoma. This case was an early and polypoid-type gastric endocrine cell carcinoma. Since examples of such cases are rare in the literature, we report this case in brief. (Dig Endosc 1998 ; 10 : 236-239)

A bstract:We have performed the immunohistochemieal analysis for PTHrP expression in norreal and 60 lung, 108 uterine, 28 breast, 42 renal, 22 ovarian and 33 gastric neoplastic tissues. Normal epithelial tissues, such as keratinocytes, renal tubules and mammary ductal cells showed positive immunoreactivity. In lung cancer, squamous (94~ and small cell (89~ carcinoma were positive regardless to the association with hypercalcemia and adenocarcinoma was negative. In uterine cervical neoplasia, 96% of squamous cell carcinoma were positive and higher immunoreactivity was observed in the cases with keratinization or prominent stromal cell interaction. 57% of brea st cancer examined were positive and immunoreactivity was most intensely observed in papillotubular and seirrhous types. Among the metastatic sites of breast cancer, skeletal lesion showed significantly higher expression of PTHrP than other sites. PTHrP was detected in 95% of renal cell carcinoma but the incidence of hypercalcemia was only 14%. In ovarian neoplasia, serous cystadenocarcinoma and clear cell carcinoma were the major histological subtypes showed positive for PTHrP. In gastric cancer, only exceptional cases of adenocarcinoma associated with heterotopic ossification showed positive for PTHrP. In conclusion, PTHrP was expressed commonly in human cancer tissues regardless to the existence of hypercalcemia. Histological subtypes were well correlated to the expression of PTHrP and surrounding tissues could modify the production of PTHrP in cancer cells.