P53 protein expression in lymphomas and reactive lymphoid tissue

Abstract

P53 is a tumour suppressor gene, located in the short arm of chromosome 17, which encodes for a nuclear protein involved in the control of cellular growth, regulating the entry of the cell into the S-phase. P53 mutations have been identified in a progressively increasing number of human malignancies. Nuclear p53 protein is usually present in non-tumour cells in minute concentrations, due to its short half-life. In contrast, tumours with p53 mRNA mutations show a higher nuclear protein concentration, detectable by immunohistological techniques, due to stabilization by complexing with other proteins such as heat-shock protein or wild-type p53 protein. Levels of nuclear p53 protein detected by immunohistochemistry with the monoclonal antibody PAb 1801 were measured with the aid of an image analysis system in 83 non-Hodgkin's lymphomas (NHLs) and 13 cases of Hodgkin's disease, as well as in 14 cases of normal thymus, reactive tonsils, and lymphadenitis. High levels of p53 protein (greater than 5 per cent of the cells) were present only in high-grade lymphomas (in the proportion 13/55), with a peak incidence in Burkitt's lymphoma (5/8 cases). Lower levels (less than 5 per cent) of p53 protein were detected in low-grade B- and T-cell lymphomas, as well as in most of the cases of Hodgkin's disease, where p53 protein was selectively present in Hodgkin and Reed-Sternberg cells. In 5/14 reactive tonsils or lymph nodes, occasional p53-positive cells were identified. These results suggest a relationship between levels of p53 protein and the aggressiveness of NHL.(ABSTRACT TRUNCATED AT 250 WORDS)

p53 and bcl-2 expression in high-grade B-cell lymphomas: correlation with survival time

“…In a separate assay, the impact of simultaneous p53 and bcl-2 expression was assessed, the relative risk being equivalent to the addition of p53 and bcl-2 relative risks. The distribution of both bcl-2 and p53 proteins in reactive lymph nodes and lymphomas has already been described (Pezzella et al, 1990(Pezzella et al, , 1993Villuendas et al, 1991Villuendas et al, , 1992. The results are similar to those found in this series, in which bcl-2 expression is more frequently detected in large B-cell lymphomas of nodal origin, and rarely in cases of Burkitt and MALT lymphoma.…”

“…However, further studies have confirmed that activated lymphoid cells may express p53, expression being dependent on cell cycle phase (M. Sanchez-Beato, submitted). p53 mutations have been described in Burkitt's lymphoma (Farrell et al, 1991;Gaidano et al, 1991;Wiman et al, 1991), and adult T-cell leukaemia/lymphoma (ATLL) (Ceserman et al, 1992) but p53 protein detection has been reported in other different types of B-cell high-grade lymphoma (Doglioni et al, 1991;Villuendas et al, 1992;Pezzella et al, 1993). A recent study relates p53 mutation to disease progression in B-cell lymphoma (Ichikawa et al, 1992).…”

Bcl-2 protein: a prognostic factor inversely correlated to p53 in non-small-cell lung cancer

“…In this series of NSCLCs the results showed that Bcl-2 and p53: (a) are detectable by the immunohistochemical technique in about 60% and 70% of cases respectively; (b) are inversely associated; and (c) provide information regarding metastasis onset and overall survival probability. Bcl-2 represents the product of the proto-oncogene involved in the 14;18 translocation; its distribution in reactive lymph nodes and lymphomas has already been described (Villeundas et al, 1992;Pezzella et al, 1993b;Piris et al, 1994). Bcl-2 expression has been observed not only in the B-lymphoma but also in different types of solid tumours such as breast (Leek et al, 1994;Silvestrini et al, 1994), prostate (Colombel et al, 1993) thyroid (Pilotti et al, 1994) and lung cancer (Pezzella et al, 1993a).…”

Linfoma de Burkitt: características clinicopatológicas, imunoistoquímicas e associação com o vírus de Epstein-Barr (EBV) em populações adulta e pediátrica em diferentes regiões geográficas no Brasil

“…Studies have shown that in some high-grade NHLs, the occurrence of positive immunostaining does not reflect point mutations in the p53 gene and vice versa. 46 Villuendas et al 47 found overexpression of p53 protein in 5 (63%) of 8 BL cases, and…”

“…This lower percentage can be explained, in part, by the cutoff of 10% used herein, while previous studies used a cutoff of 5%. 47,48 More important, we studied a far greater number than any of the prior studies, which we believe yields a more accurate representation of p53 expression in BL (at least in Brazil).…”