Published in:
01-08-2008 | Bone and Soft Tissue Sarcomas
Flow Cytometric Analysis of DNA Ploidy and S-Phase Fraction in Primary Localized Myxofibrosarcoma: Correlations with Clinicopathological Factors, Skp2 Expression, and Patient Survival
Authors:
Hsuan-Ying Huang, MD, Wen-Wei Huang, MD, Jing-Mei Wu, MS, Chiung-Kuei Huang, MS, Jun-Wen Wang, MD, Hock-Liew Eng, MD, Ching-Nan Lin, MD, Shih-Cheng Chou, MD, Shih-Chen Yu, BS, Fu-Min Fang, MD, PhD, Jen-Chieh Lee, MD, Chien-Feng Li, MD
Published in:
Annals of Surgical Oncology
|
Issue 8/2008
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Abstract
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 (≥20%) was detected in 32 of 61 interpretable cases. Skp2 overexpression (LI ≥ 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 ≥ 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).
Conclusion
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.