Effect of loss of heterozygosity of the c-kit gene on prognosis after hepatectomy for metastatic liver gastrointestinal stromal tumors.
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.
Kikuchi
Hirotoshi
H
Second Department of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan. hirotoshi_k@hotmail.com
Yamamoto
Masayoshi
M
Hiramatsu
Yoshihiro
Y
Baba
Megumi
M
Ohta
Manabu
M
Kamiya
Kinji
K
Tanaka
Tatsuo
T
Suzuki
Shohachi
S
Sugimura
Haruhiko
H
Kitagawa
Masatoshi
M
Kanai
Toshikazu
T
Kitayama
Yasuhiko
Y
Kanda
Tatsuo
T
Nishikura
Ken
K
Konno
Hiroyuki
H
D000368:Aged; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D006498:Hepatectomy; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016133:Polymerase Chain Reaction; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D016896:Treatment Outcome
D004273:DNA, Neoplasm; D019009:Proto-Oncogene Proteins c-kit