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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

  • Bone and Soft Tissue Sarcomas
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Acknowledgments

Supported by the medical research grants from Chang Gung Memorial Hospital (CMRPG83019-II, CMRPG83038) and Chi-Mei Medical Center (CMFHR 9568).

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Authors and Affiliations

  1. Departments of Pathology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan

    Hsuan-Ying Huang MD, Jing-Mei Wu MS, Hock-Liew Eng MD & Shih-Chen Yu BS

  2. Department of Family Medicine, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan

    Wen-Wei Huang MD

  3. Graduate Institute of Clinical Medical Science, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan

    Chiung-Kuei Huang MS

  4. Department of Orthopedics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan

    Jun-Wen Wang MD

  5. Department of Pathology, Chi-Mei Foundation Medical Center, 901 Chunghwa Road, Yung Kang City, Tainan County, 710, Taiwan

    Ching-Nan Lin MD & Chien-Feng Li MD

  6. Department of Pathology and Laboratory Medicine, Veterans General Hospital-Kaohsiung, Kaohsiung, Taiwan

    Shih-Cheng Chou MD

  7. Department of Radiation Oncology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan

    Fu-Min Fang MD, PhD

  8. Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan

    Jen-Chieh Lee MD

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  1. Hsuan-Ying Huang MD
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  2. Wen-Wei Huang MD
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  8. Shih-Cheng Chou MD
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  9. Shih-Chen Yu BS
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Correspondence to Chien-Feng Li MD.

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Huang, HY., Huang, WW., Wu, JM. et al. Flow Cytometric Analysis of DNA Ploidy and S-Phase Fraction in Primary Localized Myxofibrosarcoma: Correlations with Clinicopathological Factors, Skp2 Expression, and Patient Survival. Ann Surg Oncol 15, 2239–2249 (2008). https://doi.org/10.1245/s10434-008-9968-0

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  • DOI: https://doi.org/10.1245/s10434-008-9968-0

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