Flow cytometric analysis of DNA ploidy and S-phase fraction in primary localized myxofibrosarcoma: correlations with clinicopathological factors, Skp2 expression, and patient survival.
BACKGROUND
Histological assessment for prognostication of myxofibrosarcomas remains challenging. We previously reported independent prognostic value of Skp2, an oncoprotein promoting S-phase progression (Clin Cancer Res 2006;12:487-98).


METHODS
We evaluated S-phase fraction (SPF) and ploidy of myxofibrosarcomas and the association between SPF and Skp2. Flow cytometric findings were analyzed for 75 cases and correlated with clinicopathological factors, Skp2 labeling index (LI), metastasis-free survival (MeFS), and overall survival (OS).


RESULTS
Forty-seven and 28 cases were classified as diploid and nondiploid, respectively. High SPF (>or=20%) was detected in 32 of 61 interpretable cases. Skp2 overexpression (LI >or= 10%) was seen in 36 of 72 cases with scoring. Nondiploidy correlated with higher French Federation of Cancer Centers (FNCLCC) grades (P = .006), remarkable necrosis (P = .010), and Skp2 overexpression (P = .018). Noticeably, SPF was significantly related to Skp2 LI (P < .001, r = .458), FNCLCC grade, American Joint Committee on Cancer stage, and mitotic rate. Nondiploidy predicted shorter OS (P = .0045) and MeFS (P = .0489), whereas SPF >or= 20% was only associated with inferior MeFS (P = .0252). In multivariate analyses, nondiploidy independently correlated with both OS (P = .020, RR = 3.337) and MeFS (P = .013, RR = 5.780), together with Skp2 overexpression (P = .014 for OS; P = .017 for MeFS) and disease-positive margins (P = .004 for OS; P = .002 for MeFS).


CONCLUSIONS
Skp2 promotes S-phase progression in myxofibrosarcomas. SPF provides no independent prognostic usefulness; it is probably overshadowed by Skp2. Nondiploidy adds another predictive value to Skp2 overexpression and disease-positive margins in prognostication.
Department of Pathology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Hsuan-Ying
HY
Huang
Wen-Wei
WW
Huang
Jing-Mei
JM
Wu
Chiung-Kuei
CK
Huang
Jun-Wen
JW
Wang
Hock-Liew
HL
Eng
Ching-Nan
CN
Lin
Shih-Cheng
SC
Chou
Shih-Chen
SC
Yu
Fu-Min
FM
Fang
Jen-Chieh
JC
Lee
Chien-Feng
CF
Li
D000328:Adult; D000368:Aged; D000782:Aneuploidy; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D005354:Fibrosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009236:Myxosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D016196:S Phase; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D044786:S-Phase Kinase-Associated Proteins; D004247:DNA