p53 protein accumulation in lung carcinomas of patients exposed to asbestos and tobacco smoke

Our plain-English summary of p53 protein accumulation in lung carcinomas of patients exposed to asbestos and tobacco smoke, by K. Nuorva, R. Mäkitaro, E. Huhti, et al (American Journal of Respiratory and Critical Care Medicine, 1994).

The study

• Authors: K. Nuorva, R. Mäkitaro, E. Huhti, D. Kamel, K. Vähäkangas, R. Bloigu, Y. Soini, P. Pääkkö
• Journal: American Journal of Respiratory and Critical Care Medicine
• Published: 1994;150(2):528-33
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Primary lung carcinomas often carry mutations in the p53 tumor suppressor gene. Most of these mutations alter the conformation of the p53 protein into a more stable phenotype that makes it immunohistochemically detectable. Asbestos is a carcinogen that can cause deletions in chromosomes and possibly also gene mutations. In this study we examined 70 primary lung carcinomas for p53 protein accumulation using a polyclonal antihuman p53 antibody, CM-1. Patients were interviewed about their occupational and smoking history and classified according to their anamnestical asbestos exposure. Presence of asbestos bodies (AB) was evaluated from histologic samples of peripheral nontumorous lung tissue using both 5-microns-thick sections stained with Perls' iron and 30-microns-thick unstained sections. Abnormal accumulation of p53 protein was found in 36 tumors (51%), more often in patients exposed to asbestos than in patients without exposure (67% versus 40%, p = 0.027). Significant association was also noticed between the accumulation of p53 and the asbestos content of lung tissue: 35% of the p53-positive patients had more than one AB/cm2 compared with 14% of p53-negative cases (p = 0.046). Patients with strongly p53-positive tumors were heavier smokers (57.2 +/- 38.2 pack-years) than patients with p53-negative or lightly positive tumors (38.9 +/- 19.9 pack-years) (p = 0.017). Our findings indicate that both asbestos exposure and heavy smoking can cause abnormal p53 protein accumulation suggestive of mutated p53.

In plain English

This study examined tumors from 70 consecutive patients operated on for primary lung carcinoma at Oulu University Central Hospital, Finland, from 1990 to 1992. Tumors were stained for p53 build-up, which the authors describe as suggestive of mutation. Patients were interviewed about work and smoking, and asbestos bodies were counted in non-tumor lung tissue (63 patients). Fiber types were not reported. Build-up was found in 36 of 70 tumors (51%), including 20 of 30 (67%) asbestos-exposed patients versus 16 of 40 (40%) with unlikely exposure (p = 0.027; 95% confidence interval 4 to 50 percentage points). Among p53-positive patients, 12 of 34 (35%) had more than 1 asbestos body per square centimetre, versus 4 of 29 (14%) p53-negative patients (p = 0.047; 95% confidence interval 1 to 41 percentage points). No smoking difference was found by p53 status overall, but strongly positive tumors came from heavier smokers than negative or lightly positive tumors (57.2 versus 38.9 pack-years, p = 0.017). The authors concluded that both asbestos exposure and heavy smoking can cause p53 build-up suggestive of mutation, noting the small sample.

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 (immunohistochemistry) study of surgically removed lung tumors, comparing p53 protein accumulation with interview-based asbestos exposure, asbestos body counts in lung tissue, and smoking history
• Who was studied: 70 consecutive patients (61 men, 9 women; mean age 64.6 years) operated on for primary lung carcinoma at Oulu University Central Hospital, Finland, January 1990 to April 1992. Peripheral lung tissue for asbestos body counting was available for 63 of them.
• Exposure: Occupational asbestos exposure; fiber type not specified. Exposure was classified from interviews as definite (e.g. more than 10 years in construction before 1975, or more than 1 year in insulation work or asbestos product manufacturing), probable, possible or unlikely. It was also measured as asbestos bodies per square centimetre in lung tissue sections, with 1 or more per square centimetre counted as histologically significant. Cigarette smoking was measured in pack-years.
• Main results:
  • Abnormal nuclear p53 accumulation was found in 36 of 70 tumors (51%).
  • 20 of 30 (67%) patients with clinical asbestos exposure had p53-positive tumors, compared with 16 of 40 (40%) with unlikely exposure (p = 0.027; 95% CI for difference of proportions 4 to 50%).
  • 12 of 34 (35%) patients with p53-positive tumors had more than 1 asbestos body per square centimetre, compared with 4 of 29 (14%) patients with p53-negative tumors. The results text gives p = 0.047, with a 95% CI for the difference of proportions of 1 to 41%.
  • Overall, smoking did not differ between patients with p53-positive and p53-negative tumors (44.2 and 40.4 pack-years). Patients with strongly p53-positive tumors (+++ or higher) had smoked a mean of 57.2 plus or minus 38.2 pack-years, compared with 38.9 plus or minus 19.9 pack-years for patients with negative or lightly positive tumors (p = 0.017).
  • In logistic regression controlling for cigarette smoking, an asbestos body count above 1 per square centimetre gave a 3.9-fold probability of p53 accumulation (p = 0.04). Clinical asbestos exposure gave a 3-fold probability of a p53-positive tumor compared with unexposed patients (p = 0.03).
  • More than 1 asbestos body per square centimetre was found in 43% of patients with a history of asbestos exposure (groups 1 to 3), compared with 11% of those with unlikely exposure (group 4) (p = 0.005).
  • All three patients who had never smoked had p53-negative tumors.
• The authors' conclusion: The authors concluded that both asbestos exposure and heavy smoking can cause abnormal p53 protein accumulation suggestive of mutated p53. In their view, p53 accumulation, probably reflecting a p53 mutation, is a factor in asbestos- and tobacco smoke-induced carcinogenesis.
• Limitations the authors state:
  • The authors stated that the number of cases was small and that further studies are needed (said in relation to the smoking finding).
  • Asbestos body counts in tissue sections are subject to error: variation in asbestos body length, section thickness, tissue shrinkage, lung distension, and above all variation between different parts of the lung.
  • Clearance of asbestos bodies from the lung (especially with chrysotile), or individual differences in asbestos body formation, could make asbestos body counts underestimate exposure in some clinically exposed patients.

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: Carcinoma, Tumor Suppressor Gene, Asbestos Exposure, Asbestos Bodies.

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