Gut and Liver

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Expression of DOG1, PDGFRA, and p16 in Gastrointestinal Stromal Tumors

Sung Hee Jung*, Kwang Sun Suh˘Ó,˘Ô, Dae Young Kang˘Ó, Dong Wook Kangˇ×, Young-Beum Kim˘Ó, and Eun-Sun Kim˘Ó
*Department of Internal Medicine, Eulji University Hospital, Eulji University College of Medicine, ˘ÓDepartment of Pathology and ˘ÔResearch Institute for Medical Sciences, Chungnam National University School of Medicine, and ˇ×Department of Pathology, Eulji University Hospital, Eulji University College of Medicine, Daejeon, Korea
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background/Aims: The diagnosis of gastrointestinal stromal tumors (GIST) relies on the demonstration of KIT expression, but KIT expression is absent or reduced in approximately 15% of GIST. Methods: Eighty-one GISTs were diagnosed between January 1998 and December 2007 at the Department of Pathology at both Chungnam National University Hospital and Eulji University Hospital, Daejeon. Medical history, patient follow-up, and radiographic data were collected if available in the medical records. To determine diagnostic and prognostic markers for GISTs focused on PDGFRA mutation and clinicopathologic features, we analyzed 81 GIST cases for KIT, PDGFRA, DOG1, and p16 expression and for mutation of PDGFRA genes. Results: Among 81 GIST cases, 20 high risk cases (24.7%) were recurred or metastasized. Immunohistochemically, KIT was positive in 76 (93.8%), PDGFRA in 75 (92.7%), and DOG1 in 77 (95.1%). With a cutoff value of 50%, p16 expression was positive in 26 cases were positive (32.1%). A correlation between p16 expression or negative DOG1 expression and recurrence or metastasis was demonstrated (p<0.05). Four cases showed a missense mutation in exon 12 of PDGFRA gene, three of these were of epithelioid GISTs. Two cases showed a silent mutation in exon 18 of PDGFRA. Conclusions: These results indicate that the expression of DOG1 and PDGFRA is observed in a majority of GIST cases. Expression of p16 and negative DOG1 expression is predictive for development of recurrence and/ or metastasis. Even though mutation of the PDGFRA gene is frequently seen in epithelioid GISTs, a clinicopathologic correlation was not demonstrated. (Gut Liver 2011;5:171-180)
Gastrointestinal stromal tumor; Platelet-derived growth factor alpha; Mutation; DOG1; p16
Gut and Liver 2011 Jun; 5(2): 171-180
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