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Differential expression of cell-cycle regulatory proteins defines distinct classes of follicular lymphoma

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Alhejaily, Abdulmohsen, Wood, Brianne, Foster, Cheryl J., Farmer, Patricia L., Gilks, C. Blake, Brettschneider, Julia, Day, Andrew G., Feilotter, Harriet E., Baetz, Tara and LeBrun, David P. (2011) Differential expression of cell-cycle regulatory proteins defines distinct classes of follicular lymphoma. Human Pathology, Vol.42 (No.7). pp. 972-982. doi:10.1016/j.humpath.2010.10.011

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Official URL: http://dx.doi.org/10.1016/j.humpath.2010.10.011

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Abstract

Follicular lymphoma, a relatively common neoplasm of mature B lymphocytes, generally pursues an indolent clinical course. The disease is biologically heterogeneous, however, and aggressive instances associated with short survival are relatively common. Because defects in the regulation of apoptotic cell death are fundamental in follicular lymphoma pathogenesis, we hypothesized that deregulated expression of components of the Rb signaling pathway may promote cell proliferation, thereby complementing antecedent antiapoptotic mutations and producing more aggressive disease. We determined the differential expression of key cell-cycle regulatory proteins in lymphoma cells by incorporating formalin-fixed, paraffin-embedded samples from the initial, diagnostic biopsies from 127 cases of follicular lymphoma into tissue microarrays, histologic sections of which were stained by immunohistochemistry for p53, pRb, p16INK4a, and cyclin D3. The results were ascertained by visual inspection and then correlated with histopathological and clinical parameters, including overall survival. Our findings show that increased abundance of p53 or p16INK4a is associated with reduced overall survival and conventional pathological markers of tumor aggressiveness including high histologic grade. Therefore, subjective quantification of cell-cycle regulatory proteins by immunohistochemistry can identify biologically and clinically distinct subsets of follicular lymphoma cases.

Item Type: Journal Article
Divisions: Faculty of Science > Statistics
Journal or Publication Title: Human Pathology
Publisher: W.B. Saunders Co.
ISSN: 0046-8177
Official Date: July 2011
Dates:
DateEvent
July 2011Published
Volume: Vol.42
Number: No.7
Page Range: pp. 972-982
DOI: 10.1016/j.humpath.2010.10.011
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access

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