DEVELOPMENT AND PROGRESSION OF HUMAN COLONIC NEOPLASMS

人类结肠腺瘤的发生概率很高

Colonic adenomas in humans have a high probability of generating carcinomas, while hyperplastic polyps, another type of benign colonic tumor, and normal colonic epithelium have a relatively low risk. Characterization of the biochemical differences between colonic carcinomas, adenomas, hyperplastic polyps and normal epithelium might elucidate the essential features of malignancy. Malignancy is characterized by excessive proliferation, incomplete differentiation, invasion into adjacent tissues and metastases to distant organs (1), but this process is poorly understood at the molecular level. A group of genes termed oncogenes have been identified in the genomes of some tumor viruses and normal and neoplastic cells. Oncogenes have been implicated in tumorigenesis because the concentrations of one or more oncogene messages are sometimes elevated or altered in nucleotide sequence in neoplastic cells compared to those from normal cells. Moreover, some oncogenes from neoplastic cells, but not from normal cells, can transform cultured cells. Although much information about oncogene aberrations already exists, little is known about some potentially important aspects of their expression in human neoplasms. The purpose of this study is to determine: 1) whether or not primary human colonic cancers consistently express the same oncogenes; 2) if primary cancers can be distinguished from metastatic colonic cancers, adenomas, hyperplastic polyps and normal colonic mucosa by their pattern of oncogene expression; 3) whether or not expression of particular oncogenes can be correlated with progression from normal mucosa to adenoma or adenoma to carcinoma; and 4) if multiple colonic tumors arising in the same individual consistently express the same oncogenes. This information would clarify whether oncogenes were involved exclusively in the growth and differentiation alterations or whether they are also involved in invasion and metastasis. Furthermore, if histologically different neoplasms in the same person consistently expressed the same oncogenes, inherited sequence polymorphisms might be important in the induction of colonic neoplasms.