Analysis of p53 gene deletions in patients with non‐Hodgkin's lymphoma by dual‐colour fluorescence in‐situ hybridization

Abstract

The most common tumour suppressor gene altered in human cancers is p53, which is located on the short arm of chromosome 17. Structural abnormalities of the short arm and loss of chromosome 17 have been reported to confer resistance to chemotherapy in patients with non‐Hodgkin's lymphoma (NHL). Therefore we studied the incidence and prognostic value of p53 deletions in patients with NHL by fluorescence in‐situ hybridization using a 40 kb cosmid probe. Specimens obtained from 79 patients with NHL were studied. 46 patients were untreated, and 33 were previously treated. 40 tumours had indolent and 39 had aggressive histologies. p53 deletions were observed in 14 specimens (18%) in 32–90% of the cells. No statistically significant difference in the incidence of p53 deletion was observed between indolent and aggressive NHLs or between untreated and previously treated patients. However, p53 deletions were observed in three of four patients with transformed lymphoma. In the untreated patients, p53 deletion had no effect on response to therapy, time to treatment failure, or survival. We conclude that p53 deletions are uncommon in NHL, and may be frequent in patients with transformed lymphoma. In this study, p53 deletions did not influence treatment outcome or prognosis of NHL. Because monosomy 17 and 17p abnormalities have been reported to confer poor prognosis in NHL, other tumour suppressor genes on 17p should therefore be studied.

Oncogenic aberrations in the p53 pathway are associated with a high S phase fraction and poor patient survival in b‐cell non‐Hodgkin's lymphoma

“…This is in agreement with earlier studies on the prognostic value of p53 expression (Louie et al, 1995;Koduru et al, 1997), TP53 point mutation (Newcomb, 1995;Ichikawa et al, 1997;Koduru et al, 1997) and TP53 deletion (Döhner et al, 1995;Galteland et al, 1999), but one group has reported that TP53 deletions had no significant prognostic value (Clodi et al, 1997). The survival of the 6 patients with p53 expression in 15-75% of the tumor cells by IHC (negative by IB, no TP53 mutation or deletion; Table I) was not different than the survival of the other ones without any TP53/p53 aberrations, indicating that the p53 expression in a fraction of the cells in these cases is not simply aberrant p53 expression (i.e., group 4) in a subclone of the tumor.…”

p53 abnormalities in splenic lymphoma with villous lymphocytes

“…35 However, one study on a large series of patients with non-Hodgkin lymphoma found that p53 deletion did not influence treatment outcome or prognosis. 19 Our data suggest that the presence of a deletion in the p53 locus is significant for the clinical course of SLVL. Six of 7 cases with p53 deletion and no detectable mutation had progressive disease, which in 4 cases was resistant to treatment with alkylating agents.…”

“…Several studies showed a strong correlation between clinical progression and occurrence of p53 mutations, [11][12][13][14][15][16][17] but others did not. 18,19 Our aim was to establish the frequency and importance of abnormalities in p53 in SLVL. For this we screened a series of patients using fluorescence in situ hybridization (FISH) to detect loss of the p53 allele as well as immunocytochemistry and flow cytometry to examine protein expression.…”

c-MYC, RB-1, TP53, and centromere 8 and 17 copy number in B-cell non-Hodgkin's lymphomas assessed by dual-color fluorescence in situ hybridization

“…Cells with centromere counts equal to two and P1 spot number less than two in average made up 4.1% (SDϭ1.5%). These fractions, similar in unstimulated and stimulated PBL, plus three standard deviations were used as cut-off for definition of an abnormal clone (25).…”

“…TP53 deletion assessed by FISH predicted poor survival in B-CLL (24). On the other hand hemizygous TP53 deletion found by FISH did not influence treatment outcome or prognosis in a heterogeneous material of NHL analyzed by Clodi et al (25).…”