Prevalence of serum antibodies against the p53 tumor suppressor gene protein in various cancers

Angelopoulou, Katerina; Diamandis, Eleftherios P.; Sutherland, D. J.; Kellen, J; Bunting, Peter S.

doi:10.1002/ijc.2910580404

Cited by 193 publications

(135 citation statements)

References 15 publications

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“…p53 was also identi®ed by its ability to be immunoprecipitated from a variety of transformed cell lines with antibodies produced by certain tumour-bearing animals (Kress et al, 1979;Melero et al, 1979;Rotter et al, 1980). Similarly, anti-p53 antibodies were also identi®ed in sera from cancer patients (Crawford et al, 1982;Caron de Fromentel et al, 1987;Angelopoulou et al, 1994).…”

Section: Early Studies Indicate a Role Of P53 In Cell Transformationmentioning

confidence: 99%

Twenty years of p53 research: structural and functional aspects of the p53 protein

1999

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Section: Early Studies Indicate a Role Of P53 In Cell Transformationmentioning

confidence: 99%

Twenty years of p53 research: structural and functional aspects of the p53 protein

1999

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“…These proteins are known as tumour antigens (Boon and van der Bruggen, 1996). One example of tumour antigens is p53 (Angelopoulou et al, 1994;Soussi, 2000). To facilitate the identification of tumour antigens in cancer, serological analysis of recombinant cDNA expression libraries (SEREX) technology was developed (Sahin et al, 1995).…”

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Identification of heat shock protein 90 and other proteins as tumour antigens by serological screening of an ovarian carcinoma expression library

et al. 2002

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Serological screening of recombinant cDNA expression libraries has been widely used for the identification of tumour antigens in various cancer types. Identification of tumour antigens in ovarian cancer may facilitate the development of vaccine-based therapies and of disease biomarkers. The purpose of our investigation is to identify tumour antigens in ovarian cancer by using the serological analysis of recombinant cDNA expression libraries method. A recombinant ovarian carcinoma cDNA expression library was screened with ascites fluid, pooled from five ovarian cancer patients. Twelve tumour antigens encoded by known genes were isolated, including ribosomal protein S18, heat shock protein 90, JK-recombination signal binding protein, ribonucleoprotein H1, RAN binding protein 7, TG-interacting factor, eukaryotic translation initiation factor p40 subunit, human amyloid precursor protein-binding protein 1, ribosomal protein L8, CDC23, IQ motif containing GTPase activating protein 1, and ribosomal protein L3. Heat shock protein 90 was chosen for further investigation. The prevalence of hsp90 autoantibodies in ovarian cancer was determined with immunoassay. Sera from 22 normal females, 32 from ovarian cancer (22 stage III/IV, 10 stage I/II), 37 colorectal cancer, 13 breast cancer, 10 lung cancer, 20 benign gynaecologic diseases, and 10 benign breast lesions were screened. Seven (32%) stage III/IV ovarian cancer, 1 (10%) stage I/II ovarian cancer, 1 (3%) colorectal cancer, 1 (8%) breast cancer, and 1 (5%) benign gynaecologic disease sera were found to contain hsp90 autoantibodies. These data support the view that hsp90 autoantibodies are frequently found in late stage ovarian cancer. Hsp90 may, therefore, represent a novel biomarker for ovarian cancer and a candidate ovarian cancer vaccine target.

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“…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). Thus, anti-p53 antibodies may be a serological marker for malignancy.…”

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

Kressner

Glimelius²,

Bergström³

et al. 1998

Br J Cancer

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Summary Serum p53 antibody levels were analysed using an enzyme-linked immunosorbent assay in serum samples obtained before surgery from 184 consecutive patients with primary colorectal cancer. Possible associations with tumour stage and tumour differentiation and the relation to patient survival time after a median follow-up of 6 years were studied. Analysis of serum p53 antibodies in the entire material demonstrated prognostic value in univariate analysis (P = 0.02); a finding that did not remain (P = 0.07) when the Dukes' stage was included in a multivariate analysis model. When the survival analysis was restricted to the potentially cured patients in Dukes' stages A-C, the serum p53 antibody levels retained independent prognostic value (P = 0.03). No clear association with tumour differentiation was found. We conclude that analysis of serum p53 antibodies may be of value for the identification of patients with different prognoses. This may be of relevance for selection of patients for adjuvant treatment.Keywords: serum p53 antibody; colorectal cancer; tumour stage; tumour differentiation; survival; immunohistochemistry Mutations or other changes in the p53 gene -the most frequent genetic alterations found in human malignancies (Levine et al, 1991;Harris and Hollstein, 1993) -can be detected in 40-70% of all colorectal adenocarcinomas (Hollstein et al, 1991; Vogelstein and Kinzler, 1992;Hamelin et al, 1994;Chang et al, 1995). It has been reported that p53 mutations are associated with poor prognosis in colorectal cancer (Hamelin et al, 1994;Goh et al, 1995;Finkelstein et al, 1996; al, 1997), while such a relation was not observed by Dix et al (1994a). 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). Thus, anti-p53 antibodies may be a serological marker for malignancy.Recent studies have shown increased serum antibody levels against mutant p53 protein in patients with breast (Crawford et al, 1982;Davidoff et al, 1992;Schlichtholtz et al, 1992;Mudenda et al, 1994), lung (Winter et al, 1992;Schlichtholtz et al, 1994) and Immunohistochemical analysis of overexpression of p53 protein p53 protein overexpression was evaluated using an immunohistochemical method (Kressner et al, 1996). Briefly, DO-7 monoclonal antibody was used in combination with ...

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Prevalence of serum antibodies against the p53 tumor suppressor gene protein in various cancers

Cited by 193 publications

References 15 publications

Twenty years of p53 research: structural and functional aspects of the p53 protein

Twenty years of p53 research: structural and functional aspects of the p53 protein

Identification of heat shock protein 90 and other proteins as tumour antigens by serological screening of an ovarian carcinoma expression library

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

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