Special cancer microenvironment in human colonic cancer: Concept of cancer microenvironment formed by peritoneal invasion (CMPI) and implication of subperitoneal fibroblast in cancer progression

Clinical outcomes of colorectal cancer are influenced not by tumor size, but by spread into the bowel wall. Although assessment of serosal involvement is an important pathological feature for classification of colon cancer, its diagnostic consistency has been questioned. Using elastic staining, we assessed elastic laminal invasion (ELI) for more objective stratification of deep tumor invasion around the peritoneal surface. In addition, pathological characteristic features of marked tumor budding, fibrosis, and macrophage infiltration in the tumor area with ELI was elucidated. This characteristic tumor area was termed cancer microenvironment formed by peritoneal elastic laminal invasion (CMPI). We elucidated histoanatomical layer-dependent heterogeneity of fibroblast in colonic tissue. Furthermore, subperitoneal fibroblasts (SPFs) play a crucial role in tumor progression and metastasis in CMPI. Our ELI and CMPI concept contributes not only to objective pathological diagnosis, but also sheds light on biological research of special cancer microenvironments detectable in human colorectal cancers. Herein, we describe the diagnostic utility of ELI and morphological alteration in advanced colorectal cancers to determine the phenomenon that occurs when tumors invade around the peritoneal surface. Next, biological research of CMPI is reviewed to stress the importance of pathological research to establish new biological concepts.