Aberrant expression of CHFR in malignant peripheral nerve sheath tumors

• DOI: 10.1038/modpathol.3800548
• Publication Date: 2006-03-22T15:28:28Z
• Authors: Chikashi Kobayashi; Yoshinao Oda; Tomonari Takahira; Teiyu Izumi; Kenichi Kawaguchi; Hidetaka Yamamoto; Sadafumi Tamiya; Tomomi Yamada; Yukihide Iwamoto; Masazumi Tsuneyoshi
• Keywords: Adult; Aged, 80 and over; Male; 0301 basic medicine; Adolescent; Infant; Cell Cycle Proteins; Middle Aged; Immunohistochemistry; Nerve Sheath Neoplasms; Neoplasm Proteins; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Ki-67 Antigen; 0302 clinical medicine; Cell Line, Tumor; Child, Preschool; Multivariate Analysis; Humans; Female; Child; Poly-ADP-Ribose Binding Proteins; Aged

Mitotic checkpoint maintains genomic integrity before mitosis. Numerous observations have suggested that mitotic abnormalities produce chromosomal instability and aneuploidy. In MPNST, complex karyotypes showing numerical and structural aberrations have been described. 'Checkpoint with forkhead-associated domain and ring finger' (CHFR) was recently identified as defining a new early mitotic checkpoint. We examined the expression of CHFR in 96 cases of MPNST by immunohistochemical and molecular methods. We found reduced (score, < or = 3) expression of CHFR in 63 out of 96 (66%) cases of MPNST, and such alteration was significantly correlated with a high mitotic count, a high Ki-67-labeling index, and a poor prognosis. In addition, MPNST with normal karyotype showed a strong (score, =5) expression of CHFR. Our results support the assertion that CHFR functions as an inhibitor of tumor proliferation.