Alterations in the RB, p16, and cyclin D1 cell cycle control pathway in osteosarcomas

Deborah A Belchis, Christopher Gocke, J. Geradts

Research output: Contribution to journalArticle

Abstract

The retinoblastoma (RB) tumor suppressor is believed to play an important role in the pathogenesis of osteosarcomas. Loss of function of RB may occur through abrogation of the RB/p16/cyclin D1 regularity pathway. Our study evaluated the protein expression of pRB, p16, and cyclin D1 in osteosarcomas: 27 tumor specimens from 20 patients were immunostained with antibodies to pRB, p16, and cyclin D1 using the avidin-biotin method with antigen retrieval. In a subset of cases, the immunohistochemical expression of pRB was correlated with loss of heterozygosity (LOH) at the RB locus; 56% of the specimens (15/27 cases) had an altered component of the pRB/p16/cyclin D1 pathway with pRB the most frequent abnormal protein (9/27 or 33%) and p16 and cyclin D1 immunohistochemically abnormal in 2 and 3 patients, respectively. Only one protein in the pathway was abnormally expressed in any individual specimen. Absent pRB expression was associated with LOH in 7 of 15 cases (47%), while in another 8 cases pRB was expressed immunohistochemically despite LOH noted by molecular analysis. Two cases were heterozygous by molecular analysis and demonstrated positive nuclear staining. These results support the role of the RB cell cycle control pathway (pRB, p16, cyclin D1) in the pathogenesis of a subset of osteosarcomas. The results also seem to identify a subset of osteosarcomas (about one-third in our study) in which other genetic factors, including others in this pathway, may be important.

Original languageEnglish (US)
Pages (from-to)377-389
Number of pages13
JournalPediatric Pathology and Molecular Medicine
Volume19
Issue number5
StatePublished - 2000
Externally publishedYes

Fingerprint

Retinoblastoma
Cyclin D1
Osteosarcoma
Cell Cycle Checkpoints
Loss of Heterozygosity
Proteins
Avidin
Biotin
Staining and Labeling
Antigens
Antibodies
Neoplasms

Keywords

  • Cyclin D1
  • Immunohistochemistry
  • Loss of heterozygosity
  • Osteosarcoma
  • p16
  • RB
  • Retinoblastoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Pediatrics, Perinatology, and Child Health

Cite this

Alterations in the RB, p16, and cyclin D1 cell cycle control pathway in osteosarcomas. / Belchis, Deborah A; Gocke, Christopher; Geradts, J.

In: Pediatric Pathology and Molecular Medicine, Vol. 19, No. 5, 2000, p. 377-389.

Research output: Contribution to journalArticle

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