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Aberrant expression of cell-cycle regulatory proteins in human mesenchymal neoplasia.

Publication ,  Journal Article
Creager, AJ; Cohen, JA; Geradts, J
Published in: Cancer Detect Prev
2001

We previously demonstrated that approximately one-half of soft-tissue sarcomas were devoid of either pRB, the product of the retinoblastoma gene, or 16, the product of the MTS1/CDKN2 gene, while a smaller subset of aggressive mesenchymal tumors without metastatic potential did not express RB by immunohistochemistry. We now studied the expression of two additional important cell-cycle regulators, namely cyclin D1 and p53, in the same cohort of high- and low-grade lesions. In the aggregate, our data provide a comprehensive overview of the importance of cell-cycle deregulation in mesenchymal neoplasia. Paraffin sections of 58 sarcomas and 23 soft-tissue tumors of low malignant potential (STT-LMP) were reacted with monoclonal antibodies against cyclin D1 and p53, using optimized immunohistochemical staining protocols. The staining data were correlated with expression of pRB and p15 and with a variety of pathologic parameters. A total of 33 of 58 sarcomas (57%) and 9 of 23 STT-LMP (39%) overexpressed p53. Fourteen sarcomas (24%) and 4 STT-LMP (17%) overexpressed cyclin D1. There was no correlation between expression of these two genes and histologic tumor type or grade. Loss of RB and loss of p16 or overexpression of cyclin D1 were mutually exclusive events. Considering all four cell-cycle regulators, sarcomas had a significantly higher abnormality rate than did STT-LMP (P < .005). Only 10% of the sarcomas but 39% of STT-LMP showed normal expression of all four gene products. Based on our findings, overexpression of cyclin D1 and (presumably mutant) p53 appear to be among the most common molecular alterations in human mesenchymal neoplasia, and abrogation of cell-cycle control is observed in the great majority of sarcomas; it is present significantly less frequently in low-grade lesions.

Duke Scholars

Published In

Cancer Detect Prev

ISSN

0361-090X

Publication Date

2001

Volume

25

Issue

2

Start / End Page

123 / 131

Location

England

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Soft Tissue Neoplasms
  • Sarcoma
  • Retinoblastoma Protein
  • Oncology & Carcinogenesis
  • Neoplasm Proteins
  • Mutation
  • Mesoderm
  • Immunoenzyme Techniques
  • Humans
 

Citation

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ICMJE
MLA
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Creager, A. J., Cohen, J. A., & Geradts, J. (2001). Aberrant expression of cell-cycle regulatory proteins in human mesenchymal neoplasia. Cancer Detect Prev, 25(2), 123–131.
Creager, A. J., J. A. Cohen, and J. Geradts. “Aberrant expression of cell-cycle regulatory proteins in human mesenchymal neoplasia.Cancer Detect Prev 25, no. 2 (2001): 123–31.
Creager AJ, Cohen JA, Geradts J. Aberrant expression of cell-cycle regulatory proteins in human mesenchymal neoplasia. Cancer Detect Prev. 2001;25(2):123–31.
Creager, A. J., et al. “Aberrant expression of cell-cycle regulatory proteins in human mesenchymal neoplasia.Cancer Detect Prev, vol. 25, no. 2, 2001, pp. 123–31.
Creager AJ, Cohen JA, Geradts J. Aberrant expression of cell-cycle regulatory proteins in human mesenchymal neoplasia. Cancer Detect Prev. 2001;25(2):123–131.
Journal cover image

Published In

Cancer Detect Prev

ISSN

0361-090X

Publication Date

2001

Volume

25

Issue

2

Start / End Page

123 / 131

Location

England

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Soft Tissue Neoplasms
  • Sarcoma
  • Retinoblastoma Protein
  • Oncology & Carcinogenesis
  • Neoplasm Proteins
  • Mutation
  • Mesoderm
  • Immunoenzyme Techniques
  • Humans