Alterations of the p16INK4a/p14ARF pathway in clear cell sarcoma

Tomonari Takahira, Yoshinao Oda, Sadafumi Tamiya, Hidetaka Yamamoto, Kenichi Kawaguchi, Chikashi Kobayashi, Yukihide Iwamoto, Masazumi Tsuneyoshi

Research output: Contribution to journalArticle

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Abstract

Clear cell sarcoma (CCS) is a very rare soft tissue sarcoma with a polor prognosis. It has become apparent through immunohistochemical, ultrastructural, and microarray analyses that CCS is a soft tissue melanocytic neoplasm. Alterations in the p16INK4a/p14ARF gene are common in malignant melanoma, which is the prototypical melanocytic neoplasm. In the present study, we performed a clinicopathologic analysis and investigated p16 and cyclin D1 expression by immunohistochemistry in 14 cases. Furthermore, we investigated genetic changes of various tumor suppressor genes and an oncogene, including p16INK4a/p14ARF, p53, β-catenin, and APC, in 11 cases. The 5-year overall survival rate in all the patients was 33.3%. A high mitotic rate was a significant adverse prognostic factor (P=0.004). Decreased expression of p16 was observed in 4 (28.6%) of 14 cases. Overexpression of cyclin D1 was observed in 9 cases (64.3%). SSCP analysis followed by DNA direct sequencing revealed point mutations of the p16INK4a gene in 2 of 11 cases (18.2%). In addition, one case with the p14ARF mutation and 2 cases with the p53 mutation were observed. None of the cases harbored mutation of the β-catenin or APC gene. Homozygous deletion of the p16INK4a/p14ARF gene was detected in one case. Methylation-specific PCR did not reveal hypermethylation of the p16INK4a/p14ARF promoter region in any of the cases. Three cases harbored genetic alterations of the p16INK4a/p14ARF gene (27.3%). All tumors with genetic alterations of the p16INK4a/p14ARF or p53 gene showed a high mitotic rate or tumor necrosis. These alterations were cordered to be influential in the poor prognosis of CCS patients.

Original languageEnglish
Pages (from-to)651-655
Number of pages5
JournalCancer Science
Volume95
Issue number8
DOIs
Publication statusPublished - Aug 1 2004

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Clear Cell Sarcoma
Tumor Suppressor Protein p14ARF
p16 Genes
Catenins
Cyclin D1
Mutation
Soft Tissue Neoplasms
APC Genes
Single-Stranded Conformational Polymorphism
Neoplasms
p53 Genes
Microarray Analysis
Tumor Suppressor Genes
DNA Sequence Analysis
Oncogenes
Point Mutation
Genetic Promoter Regions
Sarcoma
Methylation
Melanoma

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Alterations of the p16INK4a/p14ARF pathway in clear cell sarcoma. / Takahira, Tomonari; Oda, Yoshinao; Tamiya, Sadafumi; Yamamoto, Hidetaka; Kawaguchi, Kenichi; Kobayashi, Chikashi; Iwamoto, Yukihide; Tsuneyoshi, Masazumi.

In: Cancer Science, Vol. 95, No. 8, 01.08.2004, p. 651-655.

Research output: Contribution to journalArticle

Takahira, Tomonari ; Oda, Yoshinao ; Tamiya, Sadafumi ; Yamamoto, Hidetaka ; Kawaguchi, Kenichi ; Kobayashi, Chikashi ; Iwamoto, Yukihide ; Tsuneyoshi, Masazumi. / Alterations of the p16INK4a/p14ARF pathway in clear cell sarcoma. In: Cancer Science. 2004 ; Vol. 95, No. 8. pp. 651-655.
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abstract = "Clear cell sarcoma (CCS) is a very rare soft tissue sarcoma with a polor prognosis. It has become apparent through immunohistochemical, ultrastructural, and microarray analyses that CCS is a soft tissue melanocytic neoplasm. Alterations in the p16INK4a/p14ARF gene are common in malignant melanoma, which is the prototypical melanocytic neoplasm. In the present study, we performed a clinicopathologic analysis and investigated p16 and cyclin D1 expression by immunohistochemistry in 14 cases. Furthermore, we investigated genetic changes of various tumor suppressor genes and an oncogene, including p16INK4a/p14ARF, p53, β-catenin, and APC, in 11 cases. The 5-year overall survival rate in all the patients was 33.3{\%}. A high mitotic rate was a significant adverse prognostic factor (P=0.004). Decreased expression of p16 was observed in 4 (28.6{\%}) of 14 cases. Overexpression of cyclin D1 was observed in 9 cases (64.3{\%}). SSCP analysis followed by DNA direct sequencing revealed point mutations of the p16INK4a gene in 2 of 11 cases (18.2{\%}). In addition, one case with the p14ARF mutation and 2 cases with the p53 mutation were observed. None of the cases harbored mutation of the β-catenin or APC gene. Homozygous deletion of the p16INK4a/p14ARF gene was detected in one case. Methylation-specific PCR did not reveal hypermethylation of the p16INK4a/p14ARF promoter region in any of the cases. Three cases harbored genetic alterations of the p16INK4a/p14ARF gene (27.3{\%}). All tumors with genetic alterations of the p16INK4a/p14ARF or p53 gene showed a high mitotic rate or tumor necrosis. These alterations were cordered to be influential in the poor prognosis of CCS patients.",
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AU - Oda, Yoshinao

AU - Tamiya, Sadafumi

AU - Yamamoto, Hidetaka

AU - Kawaguchi, Kenichi

AU - Kobayashi, Chikashi

AU - Iwamoto, Yukihide

AU - Tsuneyoshi, Masazumi

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AB - Clear cell sarcoma (CCS) is a very rare soft tissue sarcoma with a polor prognosis. It has become apparent through immunohistochemical, ultrastructural, and microarray analyses that CCS is a soft tissue melanocytic neoplasm. Alterations in the p16INK4a/p14ARF gene are common in malignant melanoma, which is the prototypical melanocytic neoplasm. In the present study, we performed a clinicopathologic analysis and investigated p16 and cyclin D1 expression by immunohistochemistry in 14 cases. Furthermore, we investigated genetic changes of various tumor suppressor genes and an oncogene, including p16INK4a/p14ARF, p53, β-catenin, and APC, in 11 cases. The 5-year overall survival rate in all the patients was 33.3%. A high mitotic rate was a significant adverse prognostic factor (P=0.004). Decreased expression of p16 was observed in 4 (28.6%) of 14 cases. Overexpression of cyclin D1 was observed in 9 cases (64.3%). SSCP analysis followed by DNA direct sequencing revealed point mutations of the p16INK4a gene in 2 of 11 cases (18.2%). In addition, one case with the p14ARF mutation and 2 cases with the p53 mutation were observed. None of the cases harbored mutation of the β-catenin or APC gene. Homozygous deletion of the p16INK4a/p14ARF gene was detected in one case. Methylation-specific PCR did not reveal hypermethylation of the p16INK4a/p14ARF promoter region in any of the cases. Three cases harbored genetic alterations of the p16INK4a/p14ARF gene (27.3%). All tumors with genetic alterations of the p16INK4a/p14ARF or p53 gene showed a high mitotic rate or tumor necrosis. These alterations were cordered to be influential in the poor prognosis of CCS patients.

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