title: Heterogeneity in cell proliferation and expression of p53 and bcl-2 during the indolent phase of germinal centre cell lymphoma: an explanation for clinical variability.
abstract: Germinal centre cell lymphomas (GCCL) show a wide range of clinical outcomes from persistent indolent disease to large cell transformation. To investigate possible mechanisms of this heterogeneity, a combined morphometric and immunohistological study of p53, bcl-2 and cell proliferation was carried out. There was wide variation in p53 expression between biopsies and between individual follicles in the same tumour. A similar pattern of variation was seen using the cell-cycle marker MIB1, but this did not correlate with p53 expression. Even in cases in which a t(14;18) was demonstrated by PCR, variation occurred in the number of cells expressing bcl-2. On the basis of these results, we suggest that the probability of the clonal expansion of GCCL tumour cells carrying additional genetic abnormalities depends on a complex interaction of cell proliferation with p53 and bcl-2 expression, and that this may account for variation seen in the clinical behaviour seen in this group of tumours.
authors.affiliation: Centre for Haematological Oncology, General Infirmary at Leeds.
authors.forename: S
authors.initials: S
authors.lastname: Barrans
authors.forename: J
authors.initials: J
authors.lastname: Randerson
authors.forename: P
authors.initials: P
authors.lastname: Evans
authors.forename: D
authors.initials: D
authors.lastname: Blythe
authors.forename: C
authors.initials: C
authors.lastname: Shiach
authors.forename: J A
authors.initials: JA
authors.lastname: Child
authors.forename: G
authors.initials: G
authors.lastname: Morgan
authors.forename: A S
authors.initials: AS
authors.lastname: Jack
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism; D001483:Base Sequence; D002455:Cell Division; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008223:Lymphoma / Q000378:metabolism / Q000473:pathology*; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
chemical_list: D000911:Antibodies, Monoclonal; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; C067419:CBL protein, human