The molecular epidemiology of oncoproteins. Serum p53 protein in patients with asbestosis

Our plain-English summary of The molecular epidemiology of oncoproteins. Serum p53 protein in patients with asbestosis, by K. Hemminki, R. Partanen, H. Koskinen, et al (Chest, 1996).

The study

• Authors: K. Hemminki, R. Partanen, H. Koskinen, S. Smith, W. Carney, P.W. Brandt-Rauf
• Journal: Chest
• Published: 1996;109(3 Suppl):22S-26S
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

The authors examined whether serum levels of p53 protein, a tumor suppressor gene product that accumulates in many cancers, were raised in patients with asbestosis who developed cancer. They studied a previously described cohort of 111 patients with compensable asbestosis followed at the Institute of Occupational Health in Helsinki, Finland, from 1978 to 1987. Serum samples were collected periodically between 1981 and 1987 and stored frozen. By fall 1994, the Finnish Cancer Registry showed that 38 patients had developed malignant tumors: 27 lung cancers, 3 malignant pleural mesotheliomas and 8 other cancers. Single serum samples from nine normal control subjects were also available. Samples were tested with two ELISAs, one pantropic and one mutant-specific. A value above 200 pg/mL was defined as positive. With the pantropic assay, 2 of 27 lung cancer cases (7%) were positive, compared with 0 of 3 mesotheliomas, 1 of 73 noncancer asbestosis patients (1%) and 0 of 8 normal controls. With the mutant assay, 5 of 27 lung cancer cases (19%) were positive, compared with 0 of 3, 2 of 36 (6%) and 1 of 9 (11%). These differences were not statistically significant (p>0.05). The two assays correlated (R=0.67, p<0.001). Some cases were positive years before diagnosis; one adenocarcinoma case was positive up to 7 years before. The authors concluded that further study is needed to show whether elevated serum p53 predicts cancer.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

The authors measured the p53 protein in stored blood serum from Finnish patients with compensable asbestosis. The 111 patients were followed at the Institute of Occupational Health in Helsinki from 1978 to 1987, with serum collected from 1981 to 1987. By fall 1994, 38 had developed cancers, including 27 lung cancers and 3 malignant pleural mesotheliomas. The cancer cases averaged 20 years of asbestos exposure. Nine people seen for problems not related to cancer or asbestos served as normal controls. Two blood tests were used, with a positive result arbitrarily defined as above 200 pg/mL. On one test, 2 of 27 lung cancer cases were positive, compared with 1 of 73 asbestosis patients without cancer. On the other test, the figures were 5 of 27 compared with 2 of 36. None of the 3 mesothelioma cases tested positive. These differences were not statistically significant, which the authors attributed to small numbers. One adenocarcinoma case was positive up to 7 years before diagnosis. The authors concluded that further study is needed to show whether raised serum p53 predicts cancer.

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: Laboratory analysis of banked (stored frozen) serum samples from a previously described follow-up cohort of asbestosis patients, plus a small group of normal control subjects. Serum p53 was measured with two ELISAs (a pantropic assay and a mutant-specific assay), and cancer incidence was taken from the Finnish Cancer Registry.
• Who was studied: 111 patients with compensable asbestosis followed at the Institute of Occupational Health in Helsinki, Finland, from 1978 to 1987 (serum collected 1981 to 1987; cancer follow-up through fall 1994). 38 developed malignant tumors: 27 lung cancers, 3 malignant pleural mesotheliomas and 8 other cancers. The cancer cases were mainly middle-aged to elderly white male current or ex-smokers. The study also included 9 normal control subjects (all white men, mean age 53) with single serum samples from 1993.
• Exposure: Asbestos exposure averaged 20 years among the cancer cases. The noncancer asbestosis patients were described as virtually identical in asbestos exposure. Fiber types and jobs are not stated.
• Main results:
  • Pantropic p53 assay: 2 of 27 lung cancer cases (7%) were serum-positive, compared with 0 of 3 mesotheliomas (0%), 1 of 73 noncancer asbestosis control subjects (1%) and 0 of 8 normal control subjects (0%).
  • Mutant-specific p53 assay: 5 of 27 lung cancer cases (19%) were serum-positive, compared with 0 of 3 mesotheliomas (0%), 2 of 36 noncancer asbestosis control subjects (6%) and 1 of 9 normal control subjects (11%).
  • The lung cancer cases had a higher percentage of positives than either control group, but the difference was not statistically significant (Fisher's exact test, p greater than 0.05), owing to the small numbers.
  • For some cases, serum was positive for p53 years before diagnosis. The adenocarcinoma case was consistently positive by both assays (except one borderline pantropic value in 1987) up to 7 years before diagnosis.
  • The two assays correlated: R=0.52 (p less than 0.01) for the 24 sample pairs in Table 2, and R=0.67 (p less than 0.001) for all 68 sample pairs.
  • Tumor tissue from the one available case (the lung adenocarcinoma) showed a significant (p less than 0.01) elevation of intranuclear p53 compared with negative control cells and adjacent normal lung tissue.
  • Two asbestosis control patients without cancer also had elevated serum p53. The authors noted they might develop cancer in the future.
• The authors' conclusion: The authors concluded that further study is needed to show that elevated serum p53 predicts later cancer. They suggested that a battery of serum tests might ultimately help identify the individuals at highest risk in exposed cohorts.
• Limitations the authors state:
  • Differences between groups were not statistically significant because of small numbers.
  • The normal control subjects were slightly younger than the asbestosis cohort.
  • Tumor tissue was available for immunohistochemical analysis from only one case.
  • The cutoff for a positive result (greater than 200 pg/mL) was set arbitrarily. The same cutoff was used for both assays, which partly explains why the two assays found different numbers of positives.
  • Not all tumors with p53 accumulation may release detectable p53 into the blood. Circulating anti-p53 antibodies could also speed clearance of p53 or interfere with the assay.

Topics

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

Medical terms in this study, explained in our Lexicon: Epidemiology, Tumor Suppressor Gene, Cancer Registry, Lung Cancer, Pleural Mesothelioma, Mesothelioma, Adenocarcinoma.

Related studies

• Detection of serum p53 protein in lung cancer patients — J.C. Luo, R. Zehab, et al. (1994)
• Serum oncoproteins and growth factors in asbestosis and silicosis patients — P.W. Brandt-Rauf, S. Smith, et al. (1992)
• p53 protein, EGF receptor, and anti-p53 antibodies in serum from patients with occupationally derived lung cancer — J. Schneider, P. Presek, et al. (1999)
• 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)
• Serum growth factors in asbestosis patients — Y. Li, A. Karjalainen, et al. (2009)
• Connecting molecular pathways to hereditary cancer risk syndromes — J.R. Testa, D. Malkin, et al. (2013)

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