PKCθ expression in gastrointestinal stromal tumor

Abstract

Gastrointestinal stromal tumor is characterized by a gain of function mutation of KIT gene and the expression of c-kit protein, but in 5% of cases, c-kit expression is negative although histological findings of gastrointestinal stromal tumor are most suspicious. The existence of c-kit-negative gastrointestinal stromal tumors points to the need of additional markers for making the diagnosis. In this study, we studied the expression of PKCθ and correlated their expression with other immunohistochemical profiles of gastrointestinal stromal tumors and evaluated their usability as a diagnostic marker. For this purpose, 220 gastrointestinal stromal tumors were immunohistochemically stained for PKCθ, c-kit, CD34, α-smooth muscle actin and S-100 protein. Additionally, genetic studies of KIT and PDGFRA genes were performed using c-kit-negative or PKCθ-negative cases. All the 220 masses were either PKCθ-positive or c-kit-positive. PKCθ was positive in 212 (96%) cases and c-kit was positive in 216 (98%) cases in the cytoplasm of tumor cells with a diffuse staining pattern. Out of 212 PKCθ-positive GISTs, 208 (98%) cases were c-kit-positive, 174 (82%) cases were CD34-positive, 62 (29%) cases were SMA-positive and S-100 protein was positive in 54 cases (26%). Genetic analyses on eight PKCθ-negative cases showed exon 11 mutations of KIT gene in four cases. Two PKCθ-positive and c-kit-negative GISTs showed mutations of PDGFRA gene. Our study shows that PKCθ is a useful marker and it may play a role in the development of gastrointestinal stromal tumors. Together with c-kit, PKCθ immunostaining can be used as an important diagnostic tool in the pathologic diagnosis of gastrointestinal stromal tumors with its high specificity and sensitivity. © 2006 USCAP, Inc. All rights reserved.