Open AccessAlterations of the p16 INK4a /p14 ARF pathway in clear cell sarcoma
Author(s) -
Takahira Tomonari,
Oda Yoshinao,
Tamiya Sadafumi,
Yamamoto Hidetaka,
Kawaguchi Kenichi,
Kobayashi Chikashi,
Iwamoto Yukihide,
Tsuneyoshi Masazumi
Publication year - 2004
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2004.tb03324.x
Subject(s) - biology , tumor suppressor gene , cyclin d1 , cancer research , melanoma , mutation , point mutation , sarcoma , neoplasm , gene mutation , pathology , oncogene , gene , microbiology and biotechnology , cell cycle , genetics , carcinogenesis , medicine
Clear cell sarcoma (CCS) is a very rare soft tissue sarcoma with a poor prognosis. It has become apparent through immunohis‐tochemical, ultrastructural, and microarray analyses that CCS is a soft tissue melanocytic neoplasm. Alterations in the p16 INK4a / p14 ARF 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 cy‐clin D1 expression by immunohistochemistry in 14 cases. Furthermore, we investigated genetic changes of various tumor suppressor genes and an oncogene, including p16 INK4a /p14 ARF , p53 , (‐ 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 p16 INK4a gene in 2 of 11 cases (18.2%). In addition, one case with the p14 ARF mutation and 2 cases with the p53 mutation were observed. None of the cases harbored mutation of the ( ‐catenin or APC gene. Homozygous deletion of the p1ff NK4a /p14 ARF gene was detected in one case. Methylation‐specific PCR did not reveal hy‐permethylation of the p16 INK4a /p14 ARF promoter region in any of the cases. Three cases harbored genetic alterations of the pl6 INK4a / p14 ARF gene (27.3%). All tumors with genetic alterations of the p16 INK4a /p14 ARF or p53 gene showed a high mitotic rate or tumor necrosis. These alterations were considered to be influential in the poor prognosis of CCS patients.