| Theme |
Molecular pathology of colorectal cancer for clinicians |
| Title |
Roles of growth factor/receptor system in colorectal carcinomas |
| Author |
Hiroki Kuniyasu |
Department of First Pathology, Hiroshima University School of Medicine |
| Author |
Wataru Yasui |
Department of First Pathology, Hiroshima University School of Medicine |
| Author |
Hisao Ito |
Department of First Pathology, Tottori University Faculty of Medicine |
| [ Summary ] |
Most cancer cells produce a great number of growth factors, which act in autocrine, paracrine and juxtacrine manners. The multimodal functions of growth factors control cell growth, invasion, angiogenesis, morphogenesis, cell survival and metastasis. EGF and TGF alpha act through the EGFR system and share biological activities. They are expressed in both early and advanced stages of colorectal cancer. EGF is expressed in flat type early adenocarcinoma, without an adenoma component in high frequency, whereas TGF alpha is preferrentially expressed in early adenocarcinoma with an adenoma component. The incidence of EGFR expression is clearly higher in advanced cancer than that in early cancer. Cripto expression is found in both adenoma and adenocarcinoma. The incidence of cripto expression is correlated with disease stages, as well as the atypism of adenoma. Mutation of TGF beta type II receptors in the polyadenyl tracts enables cancer cells to escape the growth suppressing effects of TGF beta in both microsatellite instable and stable colorectal cancer. TGF alpha and IL-15 produced by colon cancer induce hyperplasia, and expression of angiogenic factors in the mucosa adjacent to cancers. They provide dense neovascularity around tumors, which is associated with cancer metastasis. Ki-67 labeling index of the mucosa adjacent to cancers is an excellent preoperative marker for metastasis. |