Serum Anti-p53 Antibodies and Prognosis of Patients With Small-Cell Lung Cancer

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Abstract
Background: Some patients with cancer develop antibodies against the p53 tumor suppressor protein. The presence of these antibodies in serum has been associated with the expression of mutant p53 by the tumor and in some studies with a poorer survival. Purpose: The goals of this study were to determine the prevalence of anti-p53 antibodies in the serum of patients with newly diagnosed small-cell lung cancer (SCLC) and to assess the clinical relevance of the presence of these antibodies in the serum, particularly their relationship with tumor response to treatment and with patient survival. Methods: In this prospective study, serum was obtained from 170 patients atthe time of diagnosis of SCLC who were to subsequently receive platinumor doxorubicin-based chemotherapy at any one of four hospitals in Barcelona, Spain, from October 1991 through June 1994. Normal human sera from blood bank donors (n = 50) served as controls. The presence of anti-p53 antibodies was determined by western blot analysis with the use of purified recombinant p53 protein. As of January 1996, 96.5% of the patients had been treated and observed in the study, for a median follow-up time of 33.5 months. Survival was estimated by the Kaplan-Meier method. Cox proportional hazards regression and unconditional logistic regression analyses were conducted. All P values resulted from two-sided tests. Results: Anti-p53 antibodies were detected in the serum of 27 (16%) of the 170 patients studied. None of 50 serum samples from normal individuals contained anti-p53 antibodies. Analysis of pretreatment clinical characteristics demonstrated that a weight loss of less than 5% ( P = .025), a serum lactic acid dehydrogenase (LDH) level of less than 450 U/L ( P = .002), and limited stage disease (i.e., tumor confined to one hemithorax, with local and regional lymph node positivity for tumor cells and/or ipsilateral pleural effusion allowed) ( P < .001) were associated with a statistically significant complete response to therapy. The presence of serum anti-p53 antibodies was not associated with clinical characteristics, such as age ( P = .622), functional status ( P = 1.0), disease stage ( P =.634), complete response to treatment ( P = .572), and survival ( P = .492) or with any laboratory parameters including known prognostic factors in SCLC, such as serum sodium or LDH concentration ( P values of .731 and .246, respectively). Conclusions and Implications: The presence of anti-p53 antibodies in the serum of patients with newly diagnosed SCLC was not associated with any clinical characteristics or prognostic markers, suggesting that, in this context, the measurement of antip53 antibodies is not a useful prognostic marker. [J Natl Cancer Inst 1997;89:381-5]