Comparative analysis of p16/CDKN2, p53 and ras gene alterations in human non-small cell lung cancers, with and without associated pulmonary asbestosis

Our plain-English summary of Comparative analysis of p16/CDKN2, p53 and ras gene alterations in human non-small cell lung cancers, with and without associated pulmonary asbestosis, by I. Hayashi, N. Konishi, H. Matsuda, et al (International Journal of Oncology, 1996).

The study

• Authors: I. Hayashi, N. Konishi, H. Matsuda, T. Tsuzuki, M. Tao, Y. Kitahori, T. Tokuyama, T. Yoneda, N. Narita, Y. Hiasa
• Journal: International Journal of Oncology
• Published: 1996;8(1):85-90
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

To investigate genetic abnormalities in human non-small cell lung carcinomas (NSCLC) associated with pulmonary asbestosis as compared with nou-asbestos linked lung cancers, twenty-nine primary non-small cell lung carcinomas (NSCLC) were examined for genetic abnormalities of p16/CDKN2, p53 and ras genes by single-strand conformation polymorphism analysis of polymerase chain reaction products (PCR-SSCP) and direct sequencing. Ten specimens were obtained from autopsies in which concurrent pulmonary asbestosis was present, while 19 samples were surgical specimens from asbestosis-free patients. K-ras mutations were detected in 10% each of the cancers from both asbestosis and non-asbestosis cases. p16/CDKN2 deletions or mutations and p53 aberrations were demonstrated in 20% and 10% of tumors from asbestosis cases, whereas, 32% and 21% of the cancers, respectively, from asbestosis-free patients were positive. In conclusion, it is suggested that the enhancement of neoplasia in the lung by asbestos is not dependent on suppression of p16/CDKN2 and p53 or ras activation and therefore, that asbestosis may activate alternate tumorigenic pathways in the development of NSCLC.

In plain English

This laboratory study from Nara Medical University in Japan compared gene changes in 29 non-small cell lung cancers. Ten tumor specimens came from autopsies of people who also had pulmonary asbestosis. The other 19 were removed surgically from patients with no evidence of asbestosis. The authors used DNA analysis to look for changes in the p16/CDKN2 and p53 genes and in three ras genes (H-ras, K-ras and N-ras). They also used tissue staining to look for p53 and ras proteins. Deletions or mutations of p16/CDKN2 were found in 2 of 10 tumors (20%) in the asbestosis group and 6 of 19 (32%) in the asbestosis-free group. p53 mutations were found in 1 of 10 (10%) and 4 of 19 (21%), respectively. K-ras mutations were rare in both groups: 1 of 10 and 2 of 19. Staining for p53 protein was positive in 6 of 19 asbestosis-free tumors and in none of the asbestosis tumors. The authors noted that the asbestosis group was small. They concluded that their results suggest pathways other than those involving ras, p53 and p16/CDKN2 are linked to asbestos-associated lung 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 comparison of lung tumor specimens with and without pulmonary asbestosis. DNA analysis (PCR-SSCP and direct sequencing) covered p16/CDKN2, p53 and H-, K- and N-ras. Protein staining (immunohistochemistry) covered p53 and ras p21.
• Who was studied: 29 non-small cell lung cancer specimens obtained at Nara Medical University, Japan. 10 were from autopsies of individuals with pulmonary asbestosis and 19 were surgically removed from patients with no evidence of asbestosis. Collection dates were not given.
• Exposure: Presence or absence of pulmonary asbestosis. No fiber types, jobs or exposure doses were reported for the study subjects.
• Main results:
  • p53 protein staining was positive in 6 of 19 (31.6%) tumors from asbestosis-free patients.
  • p53 protein staining was negative in all tumors from asbestosis cases (0 of 10).
  • ras p21 protein staining was positive in 18 of 19 (94.7%) non-asbestosis tumors and 7 of 10 (70%) asbestosis tumors.
  • Homozygous p16/CDKN2 deletions were found in 1 of 10 (10%) asbestosis tumors and 4 of 19 (21%) asbestosis-free tumors.
  • Combined p16/CDKN2 alterations (deletions plus mutations) were found in 20% (2 of 10) of asbestosis tumors and 32% (6 of 19) of non-asbestosis tumors.
  • A p53 mutation was found in 1 of 10 (10%) tumors associated with asbestosis.
  • p53 mutations were found in 4 of 19 (21%) non-asbestosis tumors, all in exon 8.
  • K-ras mutations were found in 1 of 10 asbestosis tumors (10%).
  • K-ras mutations were found in 2 of 19 (10.5%) tumors from patients without asbestosis.
  • Overall, fewer mutations were detected in asbestosis-associated tumors than in non-asbestosis tumors.
• The authors' conclusion: The authors concluded that, although the samples were few, their results suggest that mechanisms or pathways other than those involving ras, p53 and p16/CDKN2 are linked to asbestos-associated non-small cell lung cancer.
• Limitations the authors state:
  • The number of asbestosis-associated tumors examined was small, so the study could not detect any unusual frequencies or combinations of mutations that could be correlated to asbestos.

Topics

Medical terms in this study, explained in our Lexicon: Non-Small Cell Lung Cancer, Asbestosis, Carcinoma, Lung Cancer.

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