Abstract
BackgroundMutations in the TP53 (Tumour Protein 53) gene can lead to expression of mutant p53 proteins that accumulate in cancer cells and can induce circulating p53 antibodies in cancer patients. Our aim was to evaluate the presence and prognostic role of these antibodies in lung cancer patients and to investigate whether they were related to p53 expression or TP53 mutations in tumour tissues.MethodsA total of 201 lung cancer patients were evaluated for p53 antibodies by ELISA (Enzyme-Linked Immunosorbent Assay) and control was obtained from 54 patients with non-malignant disorders; p53 expression was evaluated in 131 of the lung cancer patients by immunohistochemistry and TP53 mutations were then investigated in 53 tumours positively staining for p53 and in 12 tumours without p53 overexpression, whose DNA was available for direct sequencing.ResultsOur results show that 20.4% of cancer patients have positive levels of p53 antibodies, while none of the controls resulted positive. High levels of p53 expression are detected in 57.3% of cases and a significant correlation between serum p53 antibodies and high levels of p53 expression in the corresponding tumours is observed. In non-small cell lung cancer, p53 antibodies are significantly associated with poorly differentiated tumours; furthermore, high levels of p53 expression significantly correlated with squamous cell carcinoma and tumours with highest grade. Survival time of non-small cell lung cancer patients low/negative for serum p53 antibodies was significantly longer compared to patients with positive levels (p = 0.049); in particular, patients with squamous cell carcinoma, but not adenocarcinoma, low/negative for these antibodies show a significant better survival compared to serum-positive patients (p = 0.044).ConclusionsIn our study, detection of serum p53 antibodies in non-small cell lung cancer patients has been shown to be useful in identifying subsets of patients with poor prognosis. A significant correlation between the presence of serum p53 antibodies in lung cancer patients and p53 overexpression in the corresponding tumours was also observed. We did not find a significant correlation between levels of serum p53 antibodies and TP53 mutations in the corresponding tumours.
Highlights
Mutations in the Tumour protein 53 (TP53) (Tumour Protein 53) gene can lead to expression of mutant p53 proteins that accumulate in cancer cells and can induce circulating p53 antibodies in cancer patients
Our results demonstrated that 20.4% of lung cancer patients (41 out of 201) had positive levels of serum p53 antibodies (p53Abs), while none of the 54 controls resulted positive (Table 3)
19 (16 non-small cell lung cancer (NSCLC) and 3 small cell lung cancer (SCLC)) out of 22 positive for serum p53Abs resulted positive for p53 tumour overexpression (86.4%), while 56 (53 NSCLC and 3 SCLC) out of 109 low/negative for serum p53Abs were positive for p53 tumour overexpression (51.4%)
Summary
Mutations in the TP53 (Tumour Protein 53) gene can lead to expression of mutant p53 proteins that accumulate in cancer cells and can induce circulating p53 antibodies in cancer patients. In a systematic review of published studies, the frequency of serum p53Abs in most of cancer patients resulted higher than in healthy and benign controls; detection of serum p53Abs may have potential diagnostic value for different types of cancer, including lung cancer [6]. Another meta-analysis suggested that the low sensitivity of serum p53Abs limited their use in the screening of lung cancer [7]. Serum p53Abs may be useful for predicting chemosensitivity in lung cancer: serum p53Ab levels significantly decreased after neoadjuvant chemotherapy and low levels of serum p53Abs before neoadjuvant chemotherapy correlated with high objective chemoresponse rate [9]
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