Measurement and evaluation of serum anti-p53 antibody levels in patients with lung cancer at its initial presentation: a prospective study

Abstract

Summary Anti-p53 antibodies in sera are known to be products of the host immune response to mutated p53 protein, and are present in some patients with various types of cancer. In this study, we measured serum anti-p53 antibody levels in 52 patients with lung cancer and 63 normal volunteers to determine the relationship between anti-p53 antibody level and clinical features of lung cancer patients. Anti-p53 antibody level was measured by an enzyme-linked immunosorbent assay and expressed as an anti-p53 antibody index, defined as the ratio of absorption of serum sample to that of p53-positive serum. The median anti-p53 antibody index was 6.6 for lung cancer patients, and higher than that in normal volunteers (1.7) (P = 0.0000). For lung cancer patients, significant differences in index levels were found by histology (4.3, n = 25, adenocarcinoma vs 8.7. n = 18, squamous cell carcinoma vs 64.8, n = 2, large-cell carcinoma vs 9.8, n = 7, small-cell carcinoma; P= 0.0109). High anti-p53 antibody index levels were observed for both large-cell carcinoma and small-cell carcinoma. When the cut-off level was set at 7.2, determined using the twice 95% specificity level for normal volunteers, the sensitivities of anti-p53 antibodies were 46.1% for all lung cancers, 28.0% for adenocarcinoma, 55.6% for squamous cell carcinoma, 100% for large-cell carcinoma and 71.4% for small-cell carcinoma. However, there were no significant differences in index level by gender, age, smoking index, presence of previous or concomitant cancer or disease stage. Mulfivariate analysis using a logistic regression model demonstrated that histological type of tumour was a dominant factor associated with elevation of anti-p53 antibody index level (P= 0.0184). These findings suggest that serum anti-p53 antibody index level might be independent of tumour burden and the presence of previous or concomitant cancer in our series of lung cancer patients, but is clearly strongly correlated with tumour histological type.

Serum tumor-associated autoantibodies as diagnostic biomarkers for lung cancer: A systematic review and meta-analysis

“…For the studies with single autoantibody, the 31 articles (with 38 tests) included participants from 8 countries ( Table 1 ). The most studied populations were Chinese [ 35 , 45 , 65 , 75 , 79 , 85 , 87 – 92 , 94 ] and Japanese [ 68 , 77 , 82 , 83 , 89 , 96 ], followed by American [ 38 , 71 – 73 ], Italian [ 78 , 80 , 93 ], and German [ 76 , 95 ].The earliest study was from 1985, and anti-CSLEX1 antibody was the first tumor-associated autoantibody to be reported in patients with LC. The sample size of the included trials ranged from 28 to 813 individuals.…”

Proteomic mapping of p53 immunogenicity in pancreatic, ovarian, and breast cancers

“…We identified a trend between circulating AAbs to p53 and the presence of somatic tumor TP53 mutations. Further validation with a larger cohort of samples and comprehensive sequencing of distant metastatic sites is warranted (Fig. B).…”

Serum p53 antibodies: predictors of survival in small-cell lung cancer?

“…Most recently p53 mutations detectable in tumour samples have been shown to be not only an independent marker for poor outcome in resectable stage I NSCLC (Harpole, 1995), but also to correlate with nodal involvement and thus shorter survival (Marchetti et al, 1993). In NSCLC there is a prevalence of p53 antibodies of around 24% correlated with a much higher rate of p53 mutation, of the order of 60-70% (Schlichtholz et al, 1992;Winter et al, 1992;Wild et al, 1995;Komiya et al, 1997;Rosenfeld et al, 1997;Bergqvist et al, 1998;Iizasa et al, 1998;Laudanski et al, 1998;Mitsudomi et al, 1998;Segawa et al, 1998). Studies have shown a decrease in levels of p53-Abs in patients treated for lung cancer (Zalcman et al, 1998).…”