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Japanese Journal of Clinical Oncology Advance Access published online on October 7, 2009
Japanese Journal of Clinical Oncology, doi:10.1093/jjco/hyp125
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© The Author (2009). Published by Oxford University Press. All rights reserved

Pfetin as a Prognostic Biomarker in Gastrointestinal Stromal Tumor: Novel Monoclonal Antibody and External Validation Study in Multiple Clinical Facilities

Kazutaka Kikuta1,2,3, Masahiro Gotoh4, Tatsuo Kanda5, Naobumi Tochigi4,6, Tadakazu Shimoda6, Tadashi Hasegawa7, Hitoshi Katai8, Yasuhiro Shimada9, Yoshiyuki Suehara10, Akira Kawai3, Setsuo Hirohashi1 and Tadashi Kondo1

1 Proteome Bioinformatics Project, National Cancer Center Research Institute, Tokyo, Japan
2 Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan
3 Orthopedic Surgery Division, National Cancer Center Hospital, Tokyo, Japan
4 Pathology Division, National Cancer Center Research Institute, Tokyo, Japan
5 Department of Surgery, Niigata University Medical and Dental Hospital, Niigata, Japan
6 Diagnostic Pathology Division, National Cancer Center Hospital, Tokyo, Japan
7 Department of Clinical Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan
8 Department of Surgical Oncology, National Cancer Center Hospital, Tokyo, Japan
9 Gastrointestinal Oncology Division, National Cancer Center Hospital, Tokyo, Japan
10 Department of Orthopedic Surgery, Juntendo University School of Medicine, Tokyo, Japan

For reprints and all correspondence: Tadashi Kondo, Proteome Bioinformatics Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. E-mail: takondo{at}ncc.go.jp

Received June 17, 2009; accepted August 20, 2009

Objective: The clinical course of gastrointestinal stromal tumor (GIST) spans a wide spectrum from a curable disorder to a highly malignant disease that leads to metastasis and death. To develop prognostic modalities for GIST patients, we developed a mouse monoclonal antibody against pfetin, the prognostic value of which has been previously reported.

Methods: The reactivity of the monoclonal antibody against pfetin was examined by western blotting and immunohistochemistry.

Results: Western blotting demonstrated that the monoclonal antibody was specific to pfetin. The immunohistochemical study demonstrated that the 5-year disease-free survival rate was 93.2% and 94.5% for GIST patients with pfetin-positive tumors and 70.0% and 80.7% for those with pfetin-negative tumors in the 159 cases from the National Cancer Center Hospital (P < 0.0001) and in the 100 cases from Niigata University Medical and Dental Hospital (P < 0.0001), respectively. Uni- and multivariate analyses revealed that pfetin expression was a powerful prognostic factor among the clinico-pathological parameters examined.

Conclusions: These results establish pfetin as a practical prognostic marker for GIST patients after surgery. Pfetin may also present a novel therapeutic target to prevent recurrence of GIST.

Key Words: GIST • pfetin • biomarker • gastrointestinal stromal tumor • prognosis


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