title: Differential expression of cell-cycle regulatory proteins defines distinct classes of follicular lymphoma.
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, p16(INK4a), 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 p16(INK4a) 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.
authors.affiliation: Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada K7L 3N6.
authors.forename: Abdulmohsen
authors.initials: A
authors.lastname: Alhejaily
authors.forename: Brianne
authors.initials: B
authors.lastname: Wood
authors.forename: Cheryl J
authors.initials: CJ
authors.lastname: Foster
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Farmer
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.forename: Julia
authors.initials: J
authors.lastname: Brettschneider
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Day
authors.forename: Harriet E
authors.initials: HE
authors.lastname: Feilotter
authors.forename: Tara
authors.initials: T
authors.lastname: Baetz
authors.forename: David P
authors.initials: DP
authors.lastname: LeBrun
mesh_terms: D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D006801:Humans; D007150:Immunohistochemistry; D008224:Lymphoma, Follicular / Q000145:classification* / Q000175:diagnosis / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53