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Flow Cytometric Analysis of DNA Ploidy and S-Phase Fraction in Primary Localized Myxofibrosarcoma: Correlations with Clinicopathological Factors, Skp2 Expression, and Patient Survival

¹ Departments of Pathology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
² Department of Family Medicine, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan
³ Graduate Institute of Clinical Medical Science, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
⁴ Department of Orthopedics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
⁵ Department of Pathology, Chi-Mei Foundation Medical Center, 901 Chunghwa Road, Yung Kang City, Tainan County 710, Taiwan
⁶ Department of Pathology and Laboratory Medicine, Veterans General Hospital-Kaohsiung, Kaohsiung, Taiwan
⁷ Department of Radiation Oncology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
⁸ Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan

Correspondence: Address correspondence and reprint requests to: Chien-Feng Li, MD; E-mail: angelo.p{at}yahoo.com.tw

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.

Key Words: Myxofibrosarcoma • Nondiploidy • S-phase fraction • Skp2