PKCtheta expression in gastrointestinal stromal tumor.
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 PKCtheta 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 PKCtheta, c-kit, CD34, alpha-smooth muscle actin and S-100 protein. Additionally, genetic studies of KIT and PDGFRA genes were performed using c-kit-negative or PKCtheta-negative cases. All the 220 masses were either PKCtheta-positive or c-kit-positive. PKCtheta 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 PKCtheta-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 PKCtheta-negative cases showed exon 11 mutations of KIT gene in four cases. Two PKCtheta-positive and c-kit-negative GISTs showed mutations of PDGFRA gene. Our study shows that PKCtheta is a useful marker and it may play a role in the development of gastrointestinal stromal tumors. Together with c-kit, PKCtheta immunostaining can be used as an important diagnostic tool in the pathologic diagnosis of gastrointestinal stromal tumors with its high specificity and sensitivity.
Kim
Kyoung-Mee
KM
Department of Pathology, Sungkyunkwan University, Seoul, Korea.
Kang
Dong Wook
DW
Moon
Woo Sung
WS
Park
Jae Bok
JB
Park
Cheol Keun
CK
Sohn
Jin Hee
JH
Jeong
Jin Sook
JS
Cho
Mee-Yon
MY
Jin
So-Young
SY
Choi
Jong Sang
JS
Kang
Dae Young
DY
D000199:Actins / Q000032:analysis; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000276:immunology; D005069:Evaluation Studies as Topic; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011493:Protein Kinase C / Q000032:analysis* / Q000276:immunology; D000074121:Protein Kinase C-theta; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D009418:S100 Proteins / Q000032:analysis; D012680:Sensitivity and Specificity
D000199:Actins; D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D007527:Isoenzymes; D009418:S100 Proteins; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta