Altered expression of cell cycle regulators in myxofibrosarcoma, with special emphasis on their prognostic implications.
Myxofibrosarcoma/myxoid malignant fibrous histiocytoma (MFH) has continued to be considered a distinct entity even after recently published reassessments of pleomorphic sarcomas and MFH. Several cell cycle-regulated proteins have already been screened by immunohistochemistry with the aim of finding the reliable prognostic indicator of soft tissue sarcomas; however, it is still unknown whether their altered expression affects patient survival in myxofibrosarcoma. In this study, we evaluated the expression of p53, MDM2, MIB-1 (Ki-67), p21, p27, p16, cyclin A, cyclin D1, and cyclin E by immunohistochemistry in 45 cases of myxofibrosarcoma. First, we searched for possible clinicopathologic prognostic factors in 61 cases of myxofibrosarcoma for which follow-up data were available. In univariate analysis, large tumor size (> or =5 cm), deeply situated tumor, and high histological grade (grade 2 or 3) significantly decreased survival (log-rank test, P <0.05). Among 43 cases of myxofibrosarcoma for which immunohistochemical findings were available, high MIB-1 labeling index (LI) (cutoffs of 10 and 22.5 on average), high cyclin A LI (cutoffs 10% and 13.8% on average), low p21 LI (cutoffs 10 and 20.7 on average), and reduced abnormal expression of p16 were adverse prognostic factors. In multivariate analysis (Cox proportional hazards model), high mitotic rate (>15/10 high-power fields), p53 immunoreactivity (cutoff 10%), high MIB-1 LI (>22.5), low p21 LI (<20.7), and low p27 LI (<47.8 on average) were independent poor prognostic factors. Our results suggest that reduced expression of p21 could be considered a new parameter to be evaluated, along with classical clinicopathologic prognostic factors, for identifying those at high risk for myxofibrosarcoma.
Oda
Yoshinao
Y
Department of Anatomic Pathology, Graduate School of Medical Information Science, Kyushu University, Fukuoka, Japan.
Takahira
Tomonari
T
Kawaguchi
Kenichi
K
Yamamoto
Hidetaka
H
Tamiya
Sadafumi
S
Matsuda
Shuichi
S
Tanaka
Kazuhiro
K
Kinukawa
Naoko
N
Iwamoto
Yukihide
Y
Tsuneyoshi
Masazumi
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000378:metabolism*; D005260:Female; D005354:Fibrosarcoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012983:Soft Tissue Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate
D018797:Cell Cycle Proteins