KIT-Negative Gastrointestinal Stromal Tumors with Special Reference to Diagnostic Approach
YE Kim, GH Kang, CK Park, DY Kang, KM Kim. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Chungnam National University Hospital, Daejeon, Korea
Background: The pathological diagnosis of gastrointestinal stromal tumor (GIST) is based on histologic findings and immunohistochemical demonstration of KIT protein. However, KIT-negative GISTs account for ∼5% of GIST cases and cause diagnostic difficulties. Recently, in addition to CD34 and PKC-theta, DOG1 is introduced as an important immunohistochemical marker with greater sensitivity and specificity. Expression of DOG1, PKC-theta and CD34 was explored in KIT- negative GISTs to evaluate their diagnostic utility.
Design: Immunohistochemistry for DOG1, PKC-theta, CD34 and mutation analyses for KIT exon 9, 11, 13, 17 and PDGFRA exon 12, 14, 18 were performed in 26 KIT-negative GIST cases. For a control, 114 KIT-positive GISTs were used.
Results: Of 26 KIT-negative GISTs, 25 were located in the stomach and one in the rectum. The histologic subtypes included 12 spindle, 10 epithelioid, and 4 mixed types. Among 26 KIT-negative GISTs, DOG1 was positive in 21 cases (81%), PKC-theta in 24 cases (92%), and CD34 in 20 cases (77%). All KIT-negative GISTs were positive for either DOG1 or PKC-theta. However, there was no statistical significance between DOG1 expression and PKC-theta expression in the diagnosis of KIT-negative GISTs (Mcnemar test, P=0.219). Mutation analyses showed PDGFRA exon 18 mutation in 14 (54%) KIT-negative GISTs. Mutations of KIT gene were not observed. KIT-negative GISTs lacking KIT/PDGFRA mutation also expressed either DOG1 or PKC-theta. In 114 KIT-positive GISTs, DOG1, PKC-theta and CD34 was positive in 89 (78%), 95 (83%), and 76 (67%) cases, respectively. Negative for both DOG1 and PKC-theta was observed in 8 KIT-positive GISTs (7%).
Conclusions: Combination of DOG1 and PKC-theta immunohistochemistry is useful in the diagnosis of KIT-negative GISTs. Although DOG-1 is a promising marker in a subset of KIT-negative GISTs, the limitation in its sensitivity should be recognized.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 95, Monday Morning