Copy number gains on 5p15, 6p11-q11, 7p12, and 8q24 are rare in sputum cells of individuals at high risk of lung cancer

Our plain-English summary of Copy number gains on 5p15, 6p11-q11, 7p12, and 8q24 are rare in sputum cells of individuals at high risk of lung cancer, by E. Kettunen, K. Salmenkivi, K. Vuopala, et al (Lung Cancer, 2006).

The study

• Authors: E. Kettunen, K. Salmenkivi, K. Vuopala, T. Toljamo, E. Kuosma, H. Norppa, S. Knuutila, S. Kaleva, M.S. Huuskonen, S. Anttila
• Journal: Lung Cancer
• Published: 2006;54(2):169-76
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Unlabelled: Lung cancer specimens display recurrent copy number aberrations in distinguished chromosomal regions as compared with normal lung cells. Such alterations have been utilized in design of fluorescence in situ hybridization (FISH) probe sets in attempts to improve the cytological diagnosis of lung cancer. One of such probe sets, LAVysion, detects copy number changes in the centromeric region of chromosome 6 (CEP6), and regions 5p15, 8q24, and 7p12, often gained in lung cancer.

Methods: We evaluated the feasibility of the LAVysion multi-color probe set in detection of individuals at high risk of lung cancer by applying the FISH probe set on smears prepared of induced sputa obtained from 20 lung cancer patients, 43 asbestos-exposed workers, 21 heavy tobacco smokers, and 15 healthy never-smokers. The hybridized sputum smears were examined using fluorescence microscopy and the number of signals in epithelial cells was examined throughout the hybridized area. Additionally, we review here the previous studies using LAVysion probe set.

Results: The FISH probe set was slightly more sensitive than cytology alone in detecting lung cancer. No significant differences in copy number gain were found between high-risk individuals and healthy never-smokers. The proportions of individuals with copy number gains in sputa among the lung cancer patients, asbestos-exposed workers, tobacco smokers, and never-smokers were 50, 20, 12, and 27%, respectively, when three or more cells with a copy number gain detected by at least two different probes was used as the cut-off point. In comparison, the sensitivity of cytology in detecting lung cancer was 44%. In the lung cancer patients the number of abnormal cells by FISH correlated well with the cytologic atypia class (Spearman rank correlation coefficient 0.77, p<0.01). Using multivariant variance analysis, gains in CEP6, 5p15, 8q24 and 7p12 were not associated with smoking or asbestos exposure.

Conclusions: FISH did not significantly exceed the sensitivity of sputum cytology in finding lung cancers. Significant differences were not found between sputa of asbestos-exposed individuals, heavy-smokers and never-smokers. More sensitive methods are needed for the follow-up of populations at high risk of contracting lung cancer.

In plain English

This Finnish study tested whether a commercial test, LAVysion, could identify people at high risk of lung cancer from induced sputum. It detects extra copies of four chromosome regions often gained in lung cancer. Of 43 asbestos-exposed workers, 21 heavy smokers, 15 never-smokers and 20 lung cancer patients, analyzable samples came from 40, 17, 15 and 18, respectively. The article also reviewed earlier studies of the test. A person counted as above the threshold if three or more cells each showed gains with at least two probes: 8 of 40 workers (20%), 2 of 17 smokers (12%), 4 of 15 never-smokers (27%) and 9 of 18 cancer patients (50%). Sensitivity for lung cancer was 50% and specificity 81%, against 44% and 100% for sputum cytology. In a combined analysis, lung cancer was significantly associated with the gains, but smoking and asbestos exposure were not. Workers with an exposure index over 70 were more often above the threshold (6 of 19 versus 2 of 20; not statistically significant). The authors concluded that more sensitive tests are needed for following high-risk groups.

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: Comparison of a fluorescence in situ hybridization (FISH) test on induced sputum across four groups, plus a review of previous studies using the same probe set
• Who was studied: 99 people in Finland. The 43 asbestos-exposed workers (all men, 40 current smokers) were sampled at the Finnish Institute of Occupational Health in 2003 to 2004. The other 56 were sampled at Lapland Central Hospital in 2003 to 2005: 21 heavy smokers, 15 healthy never-smokers and 20 lung cancer patients. Samples from 40 asbestos-exposed workers, 17 smokers, 15 never-smokers and 18 lung cancer patients could be analyzed.
• Exposure: Occupational asbestos exposure among plumbers (23), carpenters (5), insulators (2), electricians (2) and unspecified construction workers (11). An expert-evaluated cumulative exposure index ranged from 29 to 195 among 42 workers. Four workers had asbestosis. Fiber types were not specified. Tobacco smoking was also studied.
• Main results:
  • The cut-off was three or more cells, each showing copy number gains with at least two different probes. Among analyzable samples, 20% of asbestos-exposed workers (8 of 40), 12% of smokers (2 of 17), 27% of never-smokers (4 of 15) and 50% of lung cancer patients (9 of 18) were above the threshold. The counts come from the article's case tables.
  • In the three groups without lung cancer combined, 14 of 72 cases (19%) had three or more cells with gains.
  • For detecting lung cancer, the FISH test at this cut-off had sensitivity 50% and specificity 81%.
  • Sputum cytology alone had sensitivity 44% and specificity 100% for lung cancer.
  • With a cut-off of six or more abnormal cells, FISH specificity rose to 97% but sensitivity fell to 28%.
  • Among lung cancer patients, the number of abnormal cells by FISH correlated with the cytologic atypia class (Spearman rank correlation coefficient 0.77, p less than 0.01).
  • Among asbestos-exposed workers with an exposure index over 70, 6 of 19 (32%) exceeded the threshold.
  • Among asbestos-exposed workers with an exposure index under 70, 2 of 20 (10%) exceeded the threshold. The authors called the difference between the two exposure groups suggestive (p = 0.10, one-sided Fisher's exact test) and not statistically significant.
  • In multivariate variance analysis, lung cancer was significantly associated with amplifications (p = 0.0025). Smoking and asbestos exposure were not.
• The authors' conclusion: The authors concluded that the FISH test could not distinguish heavy smokers and asbestos-exposed workers from never-smokers. They suggested using more sensitive tests than LAVysion on sputum when following high-risk groups for early lung cancer diagnosis.
• Limitations the authors state:
  • The authors said periodic follow-up samples from exposed and non-exposed people may be needed before firm conclusions can be drawn.
  • The authors said passive smoking among the never-smokers could not be ruled out.
  • The authors noted that peripherally located tumours such as adenocarcinoma may not shed cells into sputum. In two adenocarcinoma patients, neither cytology nor FISH found cancer cells.

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: Sputum, Lung Cancer, Fluorescence In Situ Hybridization (FISH), Cytology, Asbestos Exposure.

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• DNA copy number changes in familial malignant mesothelioma — V. Ascoli, Y. Aalto, et al. (2001)
• Identification of specific gene copy number changes in asbestos-related lung cancer — P. Nymark, H. Wikman, et al. (2006)
• Aberrations of chromosome 19 in asbestos-associated lung cancer and in asbestos-induced micronuclei of bronchial epithelial cells in vitro — S.T. Ruosaari, P.E. Nymark, et al. (2008)
• Gene expression and copy number profiling suggests the importance of allelic imbalance in 19p in asbestos-associated lung cancer — H. Wikman, S. Ruosaari, et al. (2007)

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