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

Abstract

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.

Pathology and Prognosis of Colonic Adenocarcinomas With Intermediate Primary Tumor Stage Between pT2 and pT3

“…[71][72][73][74][75][76] In this context, the tumor microenvironment associated with peritoneal surface invasion is thought to involve fibroblasts and inflammatory cells, which may in turn play a role in further tumor progression and metastasis. 71,73,[77][78][79] It may thus make biologic sense to regard carcinomas with tumor cells continuous to the serosal surface through a fibroinflammatory response as similar in prognosis to bona fide pT4a tumors. In contrast, destruction of the colonic wall muscle layer does not lead to ulceration or as robust an inflammatory response (there is no penetration into the peritoneal space).…”

Colonic poorly differentiated adenocarcinoma with abundant cancer‐associated fibroblasts diagnosed by trans‐gastric endoscopic ultrasound‐guided fine needle aspiration cytology

“…CAFs have activated fibroblasts with a myofibroblast‐like phenotype expressing alpha‐smooth muscle actin (α‐SMA) in cancer tissue . They are thought to play an important role in cancer progression, epithelial‐mesenchymal transition and metastasis . In the present case, CAFs appeared in the EUS‐FNA cytology specimens at a high density, with markedly enlarged hyperchromatic nuclei.…”

First-in-Human Phase 1 Trial of Agarose Beads Containing Murine RENCA Cells in Advanced Solid Tumors

“…In fact, the situation is even more complex than that. The complex and dynamic nature of cancer as a biological system dynamic arises not only from the nature of the neoplastic cell itself and the interactions among tumor cells but also from their interactions with the cells and matrix of the tumor microenvironment, 10–12 normal neighboring cells, 13,14 endothelial and other vascular cells, 15,16 the immune system, 17 and the endocrine system, 18 to name just a few parts of the system. These interactions may be autocrine, paracrine, exocrine (as with exosomes), 10,19 circulating tumor cells 20 and circulating DNA, DNA fragments, chromatin, and mRNA 21,22 (exosomal or not), 10,19 and hormonal.…”