The role of circulating anti-p53 antibodies in patients with advanced non-small cell lung cancer and their correlation to clinical parameters and survival.
BACKGROUND
Lung cancer causes approximately one million deaths each year worldwide and protein p53 has been shown to be involved in the intricate processes regulating response to radiation and/or chemotherapeutic treatment. Consequently, since antibodies against p53 (anti-p53 antibodies) are associated with mutations within the p53 gene it seems likely that these antibodies could, hypothetically, be correlated with prognosis.


METHODS
Serum samples from patients with non-small cell lung cancer (NSCLC) admitted to the Department of Oncology, University Hospital, Uppsala, Sweden, during 1983-1996 were studied. Anti-p53 abs were measured using a sandwich ELISA (Dianova, Hamburg, Germany).


RESULTS
The present study included 84 patients with stage IIIA-IV (advanced NSCLC). At least three serum samples from each patient were collected and altogether 529 serum samples were analysed for the presence of anti-p53 antibodies. The median value of anti-p53 antibodies was 0.06 (range 0 - 139.8). Seventeen percent of investigated NSCLC first serum samples (n = 84) expressed elevated levels of anti-p53 antibodies. Anti-p53 antibodies were not correlated to tumour volume or platelets. Survival analysis showed that anti-p53 antibodies were not associated with survival as revealed by univariate analysis (p = 0.29). However, patients with adenocarcinoma had a significantly poorer survival if they expressed anti-p53 antibodies (p = 0.01), whereas this was not found for patients with squamous cell carcinoma (p = 0.13). In patients where the blood samples were collected during radiation therapy, a statistically significant correlation towards poorer survival was found (p = 0.05) when elevated anti-p53 antibodies levels were present. No correlations to survival were found for serum samples collected prior to radiation therapy, during chemotherapy, or during follow-up. When anti-p53 antibodies were measured continuously, no increase in median anti-p53 values was observed the closer the individual patient come to death.


CONCLUSIONS
The result of the present retrospective study indicates that anti-p53 antibodies are not suitable for predictions concerning selection of patients with a more favourable outcome. Further prospective studies are, though, needed to fully elucidate this issue.
Bergqvist
Michael
M
Department of Oncology, University Hospital, 751 85 Uppsala, Sweden. Michael.Bergqvist@onkologi.uu.se
Brattström
Daniel
D
Larsson
Anders
A
Hesselius
Patrik
P
Brodin
Ola
O
Wagenius
Gunnar
G
D000230:Adenocarcinoma / Q000276:immunology; D000906:Antibodies / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D016019:Survival Analysis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*
D000906:Antibodies; D016159:Tumor Suppressor Protein p53