Prognostic significance of phosphorylated FOXO1 expression in soft tissue sarcoma.
BACKGROUND
Forkhead box O1 (FOXO1; forkhead in rhabdomyosarcoma, FKHR) is a key transcription factor that regulates the cell cycle and apoptosis, and therefore is considered to be involved in cell transformation and tumorigenesis. Expression of FOXO1 in soft tissue sarcoma (STS) and its correlation with clinicopathological factors and prognostic significance were evaluated.


METHODS
Expression of phosphorylated FOXO1 (p-FOXO1) in localized STS from 84 adult patients, 50 male and 34 female, aged 15-89 (median 54) years, was evaluated by immunohistochemistry. Staining intensity of p-FOXO1 in the tumors was judged separately for the nucleus and cytoplasm and categorized as follows: level 0, absent or faint staining; level 1, weaker than that of endothelial cells in the same specimen; and level 2, equal to or stronger than that of endothelial cells.


RESULTS
Twenty-three (27.3%), 26 (31.0%), and 35 (41.7%), and 32 (38.1%), 30 (35.7%), and 22 (26.2%) of the tumors showed level 0, 1, and 2 expression of p-FOXO1 for the nucleus and cytoplasm, respectively. Nuclear p-FOXO1 expression correlated with mitotic count, and cytoplasmic p-FOXO1 expression with histological subtype, mitotic count, cellularity, myxoid change, Ki-67 labeling index, histological grade, American Joint Committee on Cancer stage, and patient age. Multivariate analysis revealed nuclear and cytoplasmic p-FOXO1 expression, mitotic count, and tumor size to be independent prognostic indicators for overall survival, and cytoplasmic p-FOXO1 expression for disease-free survival, respectively.


CONCLUSIONS
The prognostic significance of p-FOXO1 expression level in STS was demonstrated.
Zhang
Binglin
B
Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Tomita
Yasuhiko
Y
Ch'ng
Eweseng
E
Qiu
Ying
Y
He
Juxiang
J
Jin
Yu-Fen
YF
Tomoeda
Miki
M
Hamada
Ken-ichiro
K
Ueda
Takafumi
T
Aozasa
Katsuyuki
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011379:Prognosis; D012509:Sarcoma / Q000378:metabolism*; D055815:Young Adult
D014408:Biomarkers, Tumor; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors