Virchows Archiv

, Volume 471, Issue 1, pp 117–122 | Cite as

HIF-1α, MDM2, CDK4, and p16 expression in ischemic fasciitis, focusing on its ischemic condition

  • Yuichi Yamada
  • Izumi Kinoshita
  • Kenichi Kohashi
  • Hidetaka Yamamoto
  • Yuki Kuma
  • Takamichi Ito
  • Kenji Koda
  • Atsushi Kisanuki
  • Manabu Kurosawa
  • Michiko Yoshimura
  • Masutaka Furue
  • Yoshinao OdaEmail author
Original Article


Ischemic fasciitis is a benign myofibroblastic lesion, occurring in the sacral region or proximal thigh of elderly or bedridden individuals. The pathogenesis of ischemic fasciitis is thought to be based on ischemic condition; however, it has never been demonstrated. In this study, we examined the expression of ischemia-associated proteins in ischemic fasciitis by immunohistochemical and genetic methods. Specifically, this study aimed to reveal the expression of HIF-1α, MDM2, CDK4, p16, and gene amplification of MDM2 gene. Seven cases of ischemic fasciitis from among the soft-tissue tumors registered at our institution were retrieved. Histopathological findings were as follows: poorly demarcated nodular masses, a proliferation of spindle-shaped fibroblastic or myofibroblastic cells with oval nuclei and eosinophilic or pale cytoplasm, zonal fibrinous deposition, pseudocystic degeneration, granulation-like proliferation of capillary vessels, ganglion-like cells, myxoid or hyalinized stroma, and chronic inflammatory infiltration. Immunohistochemically, the spindle cells were positive for HIF-1α (7/7 cases), MDM2 (4/7 cases), CDK4 (4/7 cases), p16 (7/7 cases), p53 (2/7 case), cyclin D1 (7/7 cases), and alpha-smooth muscle actin (6/7 cases). Neither MDM2 gene amplification nor USP6 gene split signal was detected in any case. Overexpression of the above proteins may be associated with the pathogenic mechanism of ischemic fasciitis. It is noted that the immunohistochemical positivity of MDM2, CDK4, and p16 do not necessarily indicate malignant neoplasm such as dedifferentiated liposarcoma.


Ischemic fasciitis Dedifferentiated liposarcoma MDM2 CDK4 p16 



This study was supported by a JSPS KAKENHI Grant (No. 25293088) and by funds from the Scholarship Program of the Takeda Science Foundation. Technical support for the experimental trials was provided by the following laboratory assistants: Motoko Tomita, Mami Nakamizo, Juri Godo, Midori Kinoshita, Hisami Matsumoto, and Noriko Aoki. We also appreciate the technical assistance from The Research Support Center, Kyushu University Graduate School of Medical Sciences.

Author contributions

Yuichi Yamada and Izumi Kinoshita performed the research and wrote the paper. Kenichi Kohashi and Hidetaka Yamamoto contributed to the research design and slide review. Yuki Kuma, Takamichi Ito, and Masutaka Furue contributed to the sample collection and research design. Yoshinao Oda designed the research and gave final approval of the manuscript. All authors critically reviewed and approved the manuscript.

Compliance with ethical standards

This study was approved by the Ethics Committee of Kyushu University (Nos. 25-111, 25-143) and conducted according to the principles embodied in the Declaration of Helsinki. Informed consent was obtained from the subjects or guardians.

Conflict of interest

The authors declare that there are no conflict of interest.

Supplementary material

428_2017_2122_MOESM1_ESM.xlsx (11 kb)
Supplementary Table 1 (XLSX 10 kb).


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Yuichi Yamada
    • 1
  • Izumi Kinoshita
    • 1
  • Kenichi Kohashi
    • 1
  • Hidetaka Yamamoto
    • 1
  • Yuki Kuma
    • 1
  • Takamichi Ito
    • 1
  • Kenji Koda
    • 2
  • Atsushi Kisanuki
    • 3
  • Manabu Kurosawa
    • 4
  • Michiko Yoshimura
    • 5
  • Masutaka Furue
    • 6
  • Yoshinao Oda
    • 1
  1. 1.Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical SciencesKyushu UniversityFukuoka-shiJapan
  2. 2.Department of PathologyFujieda Municipal General HospitalFujieda-shiJapan
  3. 3.Department of PathologyNichinan Prefectural Miyazaki HospitalNichinan-shiJapan
  4. 4.Department of PathologyNagahama City HospitalNagahama-shiJapan
  5. 5.Department of PathologyBelland HospitalSakai-shiJapan
  6. 6.Department of Dermatology, Graduate School of Medical ScienceKyushu UniversityFukuoka-shiJapan

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