Abstract
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. Multivariate 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.
Highlights
The median levels of serum anti-p53 index were 6.6 for patients with lung cancer and 1.7 for normal volunteers (Figure 1): there was a statistically significant difference between these two groups (P = 0.0000). significant differences were found between the two groups in age (P = 0.0000) and in the proportion of individuals with previous or concomitant cancer (P = 0.0027) (Table 1)
Among lung cancer patients. there were no differences in anti-p53 index level by gender (8.7. male vs 4.7. female: P = 0.1015). age (4.0. < 68 years of age vs 8.2. > 68: P = 0.1152). smoking index (3.6. smoking index < 600 vs 8.7. 2 600: P = 0.0903). presence of previous or concomitant cancer (6.9. no vs 0.6. yes: P = 0.1074). or disease stage
Significant differences in index levels were found by histology
Summary
This prospective study employed serum samples obtained from 52 patients with lung cancer and 63 normal volunteers (Table 1). Recruitment of lung cancer patients and normal volunteers was performed between October 1996 and May 1997 after written informed consent had been obtained in accordance with our institutional guidelines. The patients with lung cancer included 32 men and 20 women 68 years), whereas the normal volunteers included 29 men and 34 women (median age, 29 years). There were 32 heavy smokers (smoking index 600) in the lung cancer group. Five of the lung cancer patients had a history of diagnosis of a separate cancer more than 1 year before the diagnosis of lung cancer (uterine cancer in two patients, and tongue, bladder and rectal cancer in one patient each), and two patients (one each) had a concomitant laryngeal cancer and carcinomatous cervical lymphadenopathy with a different histological type from that of lung cancer. None of the normal volunteers had a history of cancer
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