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.
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.
Barrans
S
S
Centre for Haematological Oncology, General Infirmary at Leeds.
Randerson
J
J
Evans
P
P
Blythe
D
D
Shiach
C
C
Child
J A
JA
Morgan
G
G
Jack
A S
AS
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
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