Humoral immune response against p53 protein in patients with colorectal carcinoma

Angelopoulou, Katerina; Stratis, Michael; Diamandis, Eleftherios P.

doi:10.1002/(sici)1097-0215(19970106)70:1<46::aid-ijc7>3.0.co;2-6

Cited by 56 publications

(29 citation statements)

References 14 publications

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“…21,22 In the current study, the proportion (13%) of seropositive patients is consistent with a previous report on CRC 15 but represents a lower figure than other studies reporting positivity rates varying from 18 to 32%. 16,18,20,[23][24][25] In a previous study, 26 we reported that Taiwan had the lowest frequency of p53 mutations (31%) and the highest frameshift mutation rates among various population studies, which agrees with half of the CRC patients with a p53 mutation in the tumor having circulating p53-Abs. 3 In accordance with other studies, 18,23,25-27 in our series, we found no correlation with demographic or clinicopathologic features, except for tumor location and nodal status of the tumor.…”

Section: Discussionmentioning

confidence: 53%

“…Most studies observed that these antibodies are present with equal frequency in early-and late-stage diseases. 18 Some reported that TNM stage IV colorectal cancer was associated with a greater frequency of p53-Ab positivity. 16 The prognostic value of p53-Abs is also controversial in colorectal cancer (CRC).…”

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confidence: 99%

“…Others observed no such associations. 18 Small sample size, diversity of several ELISAs and the lack of a quantitative assay could account for the contradictory results.…”

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confidence: 99%

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Humoral response to p53 in human colorectal tumors: A prospective study of 1,209 patients

Tang

Wang

et al. 2001

Int. J. Cancer

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p53 Antibodies (p53-Abs) have been detected in the serum of a proportion of colorectal cancer (CRC) patients. It is not yet known at which stage during colorectal tumor progression p53-Abs appear in the serum. The utility of these antibodies as markers for CRC prognosis remains to be clarified. Using a quantitative enzyme-linked immunosorbent assay, we analyzed serum samples from 998 CRC patients and from 211 patients with polyp. Levels of p53-Abs were defined as negative (<10 U/L), low (10 -76 U/L) and high (>76 U/L). Overall, 13.0% of CRC patients and less than 1% of polyp patients had increased serum p53-Ab levels. High p53-Ab levels were only seen in patients with invasive carcinomas. The parameters that were significantly and independently associated with a greater frequency of high p53-Ab levels were the left colon (odds ratio [OR] ‫؍‬ 3.4; 95% CI ‫؍‬ 1.1-10.5), the rectum (OR ‫؍‬ 2.9; 95% CI, 1.0 -8.8) and advanced lymph node metastasis (OR ‫؍‬ 4.6; 95% CI, 2.2-9.6). In univariate analysis, patients with high p53-Ab levels had a shorter survival times than did those without (p ‫؍‬ 0.007). However, the significant effect disappeared in a Cox regression model adjusting for sex, age, tumor location, carcinoembryonic antigen levels, gross findings, histologic grade, mucin production and TNM stage. Thus, autoantibodies against p53 occur with tumor progression in multistep colorectal carcinogenesis and increase with advanced node metastasis. Furthermore, the seemingly adverse effect of high p53-Ab levels on the survival of CRC patients may be explained by other prognostic factors.

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Humoral response to p53 in human colorectal tumors: A prospective study of 1,209 patients

Tang

Wang

et al. 2001

Int. J. Cancer

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“…In haematological malignancies, as well as in solid tumours, natural T cell-mediated immune reactions and a humoral immunity against the autologous tumour cells have been shown (Disis et al, 1994;Topalian et al, 1994;O È sterborg et al, 1995;Somasundaram et al, 1995;Angelopoulou et al, 1997). In non-Hodgkin's lymphoma of the B-cell type, T cells of the helper and cytotoxic Tlymphocyte (CTL) phenotypes recognizing autologous tumour cell-derived immunoglobulin structures have been described (Wen & Lim, 1997).…”

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Autologous T lymphocytes may specifically recognize leukaemic B cells in patients with chronic lymphocytic leukaemia

et al. 2000

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Summary. This study analysed a naturally occurring specific cellular immunity against tumour cells in chronic lymphocytic leukaemia (CLL) patients. Five out of eight patients had blood T lymphocytes able to recognize spontaneously and specifically the autologous tumour B cells (proliferation assay). In these five patients, detection of cytokines by realtime reverse transcription polymerase chain reaction (RT-PCR) revealed that granulocyte±macrophage colony-stimulating factor (GM-CSF) was the most abundant cytokine gene expressed by the T cells that recognized the autologous tumour B cells. Other activated cytokine genes were ginterferon (IFN), interleukin (IL)-2 and tumour necrosis factor (TNF)-a, but not IL-4. This profile suggests a type 1 anti-B-CLL T-cell response. CD80 and CD54 were relatively downregulated on the native tumour B cells compared with control normal B cells. Upregulation of CD80 on the leukaemic cells was mandatory for the induction of such a specific T-cell response. CD80 and CD54 monoclonal antibodies inhibited the specific T-cell DNA synthesis proliferation. The proliferative T-cell response was either MHC class I or class II restricted (inhibition by monoclonal antibodies). The specific cytokine gene expression could be found in isolated CD4, as well as CD8, T-cell subsets. This study demonstrated the presence of a potential natural specific CD4, as well as a CD8 type 1 T-cell immunity against the leukaemic CLL tumour B cells in CLL. A further detailed analysis of the spontaneous anti-CLL T-cell immunity is warranted that may facilitate the development of effective anti-tumour vaccines in CLL.

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“…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 colorectal cancer (Houbiers et al, 1995;Angelopoulou et al, 1997). Two of the studies in breast cancer patients have indicated that the occurrence of p53 antibodies may be a useful determinant with regard to poor prognosis (Schlichtholtz et al, 1992;Mudenda et al, 1994).…”

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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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Humoral immune response against p53 protein in patients with colorectal carcinoma

Cited by 56 publications

References 14 publications

Humoral response to p53 in human colorectal tumors: A prospective study of 1,209 patients

Humoral response to p53 in human colorectal tumors: A prospective study of 1,209 patients

Autologous T lymphocytes may specifically recognize leukaemic B cells in patients with chronic lymphocytic leukaemia

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

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