Evaluation of p53 protein expression as a marker for long-term prognosis in colorectal carcinoma

Abstract

Summary~Mutation of the p53 gene is reported to be of prognostic importance in colorectal carcinomas. Immunohistochemical staining of the accumulated p53 gene product may be a simple alternative for p53 mutation analysis. Previous studies addressing the prognostic importance of p53 expression. however, yielded contradictory results. Therefore, we evaluated the importance of p53 expression as a marker for long-term prognosis in a well-characterised study population of 109 colorectal carcinomas. After antigen retrieval with target unmasking fluid (TUF). immunostaining of p53 was performed with both monoclonal antibody D07 and polyclonal antibody CMI. Objective quantification of the p53 signal was assessed by a computerised image analyser. p53 expression was higher in non-mucinous tumours than in mucinous tumours (p53 labelling index = 30% and 17% respectively, P = 0.05), and in metastatic tumours compared with non-metastatic tumours (p53 labelling index = 37% and 22% respectively, P = 0.05 Lane, 1992;Levine, 1992aLevine, , 1992bOren, 1992;Vogelstein and Kinzler, 1992). It is located on the short arm of chromosome 17 in the region 17pl3 and encodes a 53 kDa nuclear phosphoprotein that serves as a transcription factor El-Deiry et al., 1993). The p53 protein indirectly regulates cell growth and inhibits cells with mutagenic damage from entering the S-phase by arresting the cell cycle in GI, during which DNA repair can proceed.In colorectal cancer, p53 mutations are frequently accompanied by allelic loss of 17p (Baker et al., 1989;Rodrigues et al., 1990). Both p53 mutations and allelic deletion of 17p occur late in tumour progression (Baker et al., 1990) and are reported to have prognostic value after surgery (Kern et al., 1989;Laurent-Puig et al., 1992;Offerhaus et al., 1992; Hamelin et al., 1994 In the p53-tested cohort of 109 patients, there were 56 men and 53 women; the median age was 66 years (mean age 65 years, s.d. = 10 years, range 25-96 years). Twenty-two tumours were located in the caecum or ascending colon, eight in the transverse colon or splenic flexure, 46 in the descending colon or sigmoid and 33 tumours in the rectum. Tumours

p53 and Rb1 protein expression: are they prognostically useful in colorectal cancer?

“…A further study (Ofner et al, 1995) showed that there was no relationship between p53 protein expression and grade or stage parameters, such as Dukes' stage, in colorectal cancer. This finding has been reiterated (Mulder et al, 1995) in a study of 109 colorectal cancers. p53 expression was found to be more frequent in non-mucinous tumours and in metastatic tumours than in primary carcinomas.…”

Clinical and pathological associations with p53 tumour-suppressor gene mutations and expression of p21WAF1/Cip1 in colorectal carcinoma

“…In some of these studies, a positive p53 IHC was associated with shortened survival (Starzynska et al, 1992;Auvinen et al, 1994), although the effect was weak or absent in others (Scott et al, 1991;Bell et al, 1993). We have previously reported a similar study in which we did not find an association between p53 IHC and survival (Mulder et al, 1995). In all these studies, the methods used to detect p53 protein were similar, although different antibodies for p53 were employed.…”

“…Exons 5 -8 were amplified separately by polymerase chain reaction (PCR) using primers and conditions as described elsewhere (DiGiuseppe et al, 1994). Mutations in the p53 gene were identified by analysing the PCR products by denaturing gradient gel electrophoresis (DGGE) as described previously (DiGiuseppe et al, 1994;Hamelin et al, 1993 (Baas et al, 1995;Kessis et al, 1993).…”

Increased serum p53 antibody levels indicate poor prognosis in patients with colorectal cancer

“…Overexpression of the p53 protein is detectable in 30-70% of the tumours using immunohistochemistry. In some studies (Remvikos et al, 1992; Sun et al, 1992;Auvinen et al, 1994;Bosari et al, 1994) p53 protein overexpression has been shown to correlate to patient survival, while this has not been confirmed in other studies (Bell et al, 1993; Baas et al, 1994;Dix et al, 1994a;Morrin et al, 1994;Mulder et al, 1995;Kressner et al, 1996Poller et al, 1997).…”

“…Overexpression of the p53 protein is detectable in 30-70% of the tumours using immunohistochemistry. In some studies (Remvikos et al, 1992; Sun et al, 1992;Auvinen et al, 1994;Bosari et al, 1994) p53 protein overexpression has been shown to correlate to patient survival, while this has not been confirmed in other studies (Bell et al, 1993; Baas et al, 1994;Dix et al, 1994a;Morrin et al, 1994;Mulder et al, 1995;Kressner et al, 1996Poller et al, 1997).Mutant p53 protein, and other tumour-specific antigens, may be a target of the host's immune response (Schlichtholtz et al, 1992;Mudenda et al, 1994). Studies have shown that 9-26% of patients with different carcinomas have mounted a humoral immune response (antibodies) to abnormal p53 protein (Caron de Fromental et al, 1987;Levine et al, 1991;Angelopoulou et al, 1994).…”