Immunohistochemical analysis of IQGAP1 expression in human colorectal carcinomas: its overexpression in carcinomas and association with invasion fronts.

In histopathological sections, it is frequently observed that carcinoma cells move in and invade the stroma as coherent cell nests, rather than single cells. We have called this type of movement 'cohort migration (CM)' and developed an in vitro model, in which human colon adenocarcinoma cells move as coherent cell sheets when stimulated with naturally occurring motogenic factor, hepatocyte growth factor/scatter factor (HGF/SF). In this CM model, localized release from cell-cell adhesion is essential for cell movement. Recently, we have shown that IQGAP1, a target molecule of Cdc42 and Rac1 small GTPases, is involved in this localized release from the E-cadherin-based cell-cell adhesion during CM. In this study, we examined expression of IQGAP1 immunohistochemically in human colorectal tissues and found that IQGAP1 was overexpressed in carcinoma tissues compared with normal counterparts. Within the carcinoma tissue, IQGAP1 tended to be expressed more at the invasion front than at the upper portions, and higher levels of expression were observed in deeper two-thirds of carcinoma tissues than in the superficial one-third. This expression pattern showing stronger signals in deeper portions was most apparent in advanced carcinomas that invaded into the subserosa. These findings supported a role of IQGAP1 in colon carcinoma invasion.