Effect of loss of heterozygosity of the c-kit gene on prognosis after hepatectomy for metastatic liver gastrointestinal stromal tumors |
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Authors: | Kikuchi Hirotoshi Yamamoto Masayoshi Hiramatsu Yoshihiro Baba Megumi Ohta Manabu Kamiya Kinji Tanaka Tatsuo Suzuki Shohachi Sugimura Haruhiko Kitagawa Masatoshi Kanai Toshikazu Kitayama Yasuhiko Kanda Tatsuo Nishikura Ken Konno Hiroyuki |
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Affiliation: | Second Department of Surgery,;Department of Endoscopic and Photodynamic Medicine,;First Department of Pathology and;Department of Biochemistry 1, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192;;Department of Surgery, Hamamatsu Medical Center, 328 Tomitsuka-cho, Naka-ku, Hamamatsu 432-8580;;Department of Pathology, Shizuoka Saiseikai General Hospital, 1-1-1 Oshika, Suruga-ku, Shizuoka 422-8527;;Division of Digestive and General Surgery and;Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata 951-8510, Japan |
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Abstract: | The authors have previously reported that loss of heterozygosity (LOH) of the c-kit gene could be responsible for the gain in high proliferative activity in some gastrointestinal stromal tumors (GIST), resulting in enhanced metastatic potential. In the present study, an attempt was made to identify the factors that might predict the postoperative prognosis of patients with metastatic liver GIST. The clinicopathologic or genetic features of resected liver GIST in 14 patients who had undergone a hepatectomy for metachronous liver metastases and who had not received adjuvant imatinib treatment were examined. LOH of the c-kit gene was observed in seven of 12 metastatic liver GIST (58.3%), of which DNA suitable for testing could be extracted. Ten patients had recurrence after hepatectomy and four had none. The median post-recurrent disease-free survival (PRDFS) after hepatectomy was 27.5 months (range 8–104). The tumor-specific PRDFS was examined using clinicopathologic features, c-kit mutation and LOH of the c-kit gene. No single clinicopathologic or genetic finding was significantly associated with PRDFS. However, patients with 'Ki67 labeling index <5% and LOH(–)' had a significantly longer PRDFS than those with 'Ki67 ≥5% or LOH(+)' ( P = 0.032), and there was no correlation between the presence of LOH of the c-kit gene and the Ki67 labeling index. LOH of the c-kit gene in metastatic liver seems to be a common event, and LOH of the c-kit gene in resected liver GIST may be a helpful factor in the prediction of the post-recurrent prognosis of patients with liver metastasis. ( Cancer Sci 2007; 98: 1734–1739) |
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