Detection of serum p53 protein in lung cancer patients

Our plain-English summary of Detection of serum p53 protein in lung cancer patients, by J.C. Luo, R. Zehab, S. Anttila, et al (Journal of Occupational Medicine., 1994).

The study

• Authors: J.C. Luo, R. Zehab, S. Anttila, M. Ridanpaa, K. Husgafvel-Pursiainen, H. Vainio, W. Carney, I. De Vivo, C. Milling, P.W. Brandt-Rauf
• Journal: Journal of Occupational Medicine.
• Published: 1994;36(2):155-60
• Cited by: 49 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Serum levels of p53 protein were examined in 23 cases of lung cancer (many with potential asbestos exposure), 23 unexposed matched hospital control subjects, 58 unmatched general population control subjects, and 4 people with nonmalignant lung disease using an enzyme-linked immunosorbent assay and Western immunoblotting. Average levels of serum p53 in the lung cancer patients (0.55 ng/mL) were higher than in the cases of nonmalignant lung disease (0.42 ng/mL) or in the matched (0.32 ng/mL) or unmatched (0.31 ng/mL) control subjects, but the differences were not statistically significant. However, three of the cases of lung cancer (13%) were found to have serum p53 levels much greater than those of the control subjects (> 2 SD above the mean) and to have confirmatory positive Western blots for p53. The tumors from these subjects demonstrated increased levels of p53 in the tissue by immunohistochemistry and/or the presence of mutations in the p53 gene. These results suggest that p53 protein can be detected in serum in a portion of lung cancer cases with p53 alterations in the tumor tissue.

In plain English

This laboratory study measured the protein p53 in blood serum. The authors tested 23 lung cancer patients operated on in Helsinki, on average elderly male smokers with definite to possible past asbestos exposure. They also tested 4 patients with nonmalignant lung disease, 23 matched hospital patients in New York with no known asbestos exposure, and 58 healthy volunteers. Average serum p53 was 0.55 ng/mL in the lung cancer patients, 0.42 in the nonmalignant group, 0.32 in matched controls and 0.31 in volunteers. These differences were not statistically significant. Three cancer patients (13%) had levels more than 2 standard deviations above the matched-control average, confirmed by a second test (Western blot). Their tumors showed raised p53 and/or p53 gene mutations. Other patients with such tumor changes did not have raised serum levels. A table listed each cancer patient's asbestos exposure category beside their serum result, but the authors did not compare serum p53 across exposure groups. The authors concluded that raised serum p53 may be detectable in some lung cancer cases with tumor p53 changes, but called the results preliminary.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Small laboratory comparison study: serum p53 levels (measured by ELISA and confirmed by Western blot) in lung cancer patients versus control groups, compared with tumor tissue staining and p53 gene mutation analysis
• Who was studied: 23 lung cancer patients (squamous cell, adeno- and small cell carcinomas) and 4 patients with nonmalignant lung disease (two tuberculosis, one pleural fibrosis, one hamartoma), drawn from 63 consecutive patients operated on for a pulmonary tumor at Helsinki University Central Hospital since 1988. Controls: 23 non-asbestos-exposed noncancer hospital patients at Columbia-Presbyterian Medical Center, matched 1:1 on age, sex and race, and 58 unmatched healthy volunteers from that center's employees and staff.
• Exposure: Asbestos exposure (fiber type not specified) and cigarette smoking. The lung cancer patients were on average smokers with definite to possible past asbestos exposure. The table rates the cases as 13% definite, 39% probable, 22% possible and 26% unlikely exposure, and lists each patient's category beside their serum p53 result. Both control groups had no known asbestos exposure. The authors did not analyze or compare serum p53 by exposure category.
• Main results:
  • Average serum p53 was 0.55 ng/mL (SD 1.16, range nondetectable to 4.48) in the 23 lung cancer patients and 0.42 ng/mL (SD 0.49) in the 4 nonmalignant lung disease patients. It was 0.32 ng/mL (SD 0.49, range nondetectable to 1.29) in the 23 matched controls and 0.31 ng/mL (SD 0.41, range nondetectable to 2.30) in the 58 unmatched controls. The differences were not statistically significant.
  • Three of the 23 lung cancer patients (13%; patients 6, 10 and 22) had serum p53 by ELISA well above 2 SD over the matched-control mean (4.48, 3.29 and 2.08 ng/mL). Western blots confirmed this, giving 4.1, 2.2 and 1.2 ng/mL.
  • Among these three, the tumors of patients 6 and 10 stained positively for increased p53, and tumor DNA from patients 6 and 22 showed hot spot mutations in the p53 gene. DNA analysis for patient 10 had been completed for only two of four regions.
  • Overall, 8 of 22 lung cancer tissues (36%) were positive for increased p53 protein and 9 of 22 (41%) were positive for p53 gene mutations.
  • Six other cancer patients had increased tumor p53 by staining, and seven had p53 gene mutations in their tumors. None of them had elevated serum p53.
• The authors' conclusion: The authors concluded that elevated serum p53 may be detectable in a proportion of lung cancer cases with p53 alterations in tumor tissue, but that the results should be considered preliminary pending further validation studies.
• Limitations the authors state:
  • Recovery by ELISA of known amounts of p53 added to normal serum is incomplete (sometimes as low as 10 to 60%), which could cause false-negative results.
  • Circulating antibodies to p53 in cancer patients could speed removal of the protein from the blood or otherwise reduce detection, causing false negatives.
  • Mismatches between tissue staining and DNA results may reflect mutations not covered by the analysis, poor preservation of p53 in formalin-fixed tissue, or sampling error.
  • Further study is needed to resolve these discrepancies and to examine other potential confounders of serum p53 levels.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Asbestos Exposure, Immunohistochemistry.

Related studies

• Serum levels of pantropic p53 protein and EGF-receptor, and detection of anti-p53 antibodies in former uranium miners (SDAG Wismut) — J. Schneider, P. Presek, et al. (1999)
• The molecular epidemiology of oncoproteins. Serum p53 protein in patients with asbestosis — K. Hemminki, R. Partanen, et al. (1996)
• p53 protein, EGF receptor, and anti-p53 antibodies in serum from patients with occupationally derived lung cancer — J. Schneider, P. Presek, et al. (1999)
• Gender comparisons in human lung cancer: analysis of p53 mutations, anti-p53 serum antibodies and C-erbB-2 expression — D.G. Guinee, W.D. Travis, et al. (1995)
• Development of an enzyme-linked immunosorbent assay for the detection of human calretinin in plasma and serum of mesothelioma patients — I. Raiko, I. Sander, et al. (2010)
• p53 protein accumulation in lung carcinomas of patients exposed to asbestos and tobacco smoke — K. Nuorva, R. Mäkitaro, et al. (1994)

Browse more research in Journal of Occupational Medicine., or return to medical research.