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Alterations of the p16INK4a/p14ARF pathway in clear cell sarcoma

Tomonari Takahira1, Yoshinao Oda, Sadafumi Tamiya

  • 1Department of Anatomic Pathology (Second Department of Pathology), Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.

Cancer Science
|August 10, 2004
PubMed

Insights

Clear cell sarcoma (CCS), a rare cancer, is a melanocytic neoplasm. Genetic alterations in tumor suppressor genes like p16INK4a/p14ARF and p53 are linked to poor prognosis in CCS patients.

Area of Science:

  • Oncology
  • Genetics
  • Pathology

Background:

  • Clear cell sarcoma (CCS) is a rare soft tissue malignancy with a poor prognosis.
  • Recent analyses indicate CCS is a soft tissue melanocytic neoplasm.
  • Alterations in the p16INK4a/p14ARF gene are characteristic of malignant melanoma.

Purpose of the Study:

  • To conduct a clinicopathologic analysis of CCS.
  • To investigate the expression of p16 and cyclin D1.
  • To examine genetic alterations in tumor suppressor genes (p16INK4a/p14ARF, p53, beta-catenin, APC) and an oncogene in CCS.

Main Methods:

  • Clinicopathologic analysis of 14 CCS cases.
  • Immunohistochemistry for p16 and cyclin D1 expression.
  • Analysis of genetic alterations including point mutations, homozygous deletion, and promoter methylation of key genes in 11 CCS cases.

Main Results:

  • The 5-year overall survival rate was 33.3%.
  • High mitotic rate was a significant adverse prognostic factor.
  • Decreased p16 expression (28.6%), cyclin D1 overexpression (64.3%), and genetic alterations in p16INK4a/p14ARF (27.3%) and p53 (18.2%) were observed. None had beta-catenin or APC mutations.

Conclusions:

  • Genetic alterations in p16INK4a/p14ARF and p53 are associated with aggressive features like high mitotic rate and tumor necrosis in CCS.
  • These genetic changes are likely influential factors contributing to the poor prognosis observed in clear cell sarcoma patients.

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