DNA analysis by flow cytometry in malignant pleural mesothelioma: relationship to histology and survival

Our plain-English summary of DNA analysis by flow cytometry in malignant pleural mesothelioma: relationship to histology and survival, by H. Dazzi, N. Thatcher, P.S. Hasleton, et al (The Journal of Pathology, 1990).

The study

• Authors: H. Dazzi, N. Thatcher, P.S. Hasleton, A.K. Chatterjee, R.A. Lawson
• Journal: The Journal of Pathology
• Published: 1990;162(1):51-5
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher
• In J-M's library: Johns-Manville's company medical library held a copy (J-M no. 004916).

Abstract

In a retrospective study of 70 patients with malignant pleural mesothelioma, 168 formalin-fixed, paraffin-embedded tumour specimens were examined for DNA content by flow cytometry. In 20 patients where two or more blocks of the same tumour were available, there was considerable agreement between ploidy status and S-phase percentage in the different specimens. There were no significant differences for survival for patients who had been exposed to asbestos and those in whom no exposure could be elicited, nor for aneuploid and diploid tumours. The S-phase content was examined for different areas of the same tumour and the percentages were largely in agreement. However, those patients who had tumours with an S-phase percentage greater than the median (6 per cent) had a significantly shorter survival than those with tumours of lower S-phase percentage. Differences in DNA content and other cell cycle parameters were not associated with the histological subtypes.

In plain English

This retrospective study examined tumour tissue from 70 patients with malignant pleural mesothelioma. Using flow cytometry, the authors measured DNA content in 168 tumour blocks and compared it with tumour type, asbestos exposure history and survival. Of all tumours, 38.6 per cent were diploid (normal DNA amount) and 61.4 per cent aneuploid (abnormal amount), with no significant difference by tumour type. Asbestos exposure was reported for 71 per cent of diploid and 53 per cent of aneuploid tumours, a difference that was not statistically significant. Survival did not differ significantly between patients with a reported asbestos exposure and those in whom none could be elicited, nor between diploid and aneuploid tumours. The authors linked a high S-phase percentage to rapidly dividing cells. Patients whose tumours had an S-phase percentage below 6 per cent survived significantly longer (median 122.4 weeks) than those above 6 per cent (median 66.8 weeks). After allowing for tumour type, this difference fell short of significance (P = 0.06). The authors concluded that aneuploidy did not appear to be a significantly adverse survival factor.

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: Retrospective laboratory study of archived tumour specimens, with DNA content measured by flow cytometry and compared with histology and survival
• Who was studied: 70 patients with malignant pleural mesothelioma (63 males, 7 females, mean age 61.5 years). 168 tumour blocks were examined, obtained at autopsy (36 patients), at thoracotomy (29 patients), or at both (5 patients). Histological types were epithelial in 31, sarcomatous in 21 and mixed cell in 18. The article does not state where or when the patients were seen.
• Exposure: History of asbestos exposure, recorded as a positive history or no exposure elicited. Fiber types, jobs and doses were not reported. The main measurements were tumour DNA content (ploidy), S-phase percentage and proliferation index.
• Main results:
  • Of all tumours, 38.6 per cent were diploid and 61.4 per cent aneuploid.
  • The pattern of DNA content did not vary significantly between histological subgroups (P = 0.60). There was a trend for more diploid tumours among the epithelial type (45.2 per cent) than in the other two types (33.3 per cent each).
  • A positive asbestos exposure history was found in 71 per cent of patients with diploid tumours versus 53 per cent with aneuploid tumours. This difference was not statistically significant (P greater than 0.05).
  • There was no significant survival difference between patients who had been exposed to asbestos and those in whom no exposure could be elicited.
  • There was no significant survival difference between patients with aneuploid and diploid tumours (P = 0.4), nor by proliferation index (P = 0.75).
  • The S-phase percentage could be calculated in 79 per cent of patients (55 patients). The median was 6 per cent, with a range of 0.8 to 16.1 per cent.
  • Patients with tumours with an S-phase percentage below 6 per cent survived significantly longer (median 122.4 weeks; P = 0.02) than patients with tumours above 6 per cent (median 66.8 weeks).
  • The authors described a high S-phase percentage as indicating a large number of rapidly proliferating cells.
  • When histological subgroup was taken into account, the survival difference for S-phase percentage was reduced to P = 0.06.
  • Survival differed overall between the three histological subgroups (P = 0.03). Nine epithelial, three sarcomatous and one mixed cell patient survived 2 years or more.
  • In the five patients with both thoracotomy and autopsy specimens, results agreed completely in four.
• The authors' conclusion: The authors concluded that aneuploidy did not appear to be a significantly adverse survival factor. In their view, the S-phase percentage gave additional information in advanced disease that was not provided by histological subgroup. They suggested that further studies of asbestos exposure, ploidy, histology and prognosis would be of interest.
• Limitations the authors state:
  • Flow cytometry cannot tell normal from cancerous cells with normal DNA content. It cannot exclude a diploid tumour population alongside an aneuploid one, and it does not detect gains or losses of single chromosomes.
  • The S-phase percentage could be calculated in only 55 patients, because in highly aneuploid tumours the overlapping cell populations did not form distinct peaks.
  • Samples that remained of low quality after repeat analysis (approximately 10 per cent) were excluded from the study.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Histology, Histological Subtype.

Related studies

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• Prognostic significance of flow cytometric DNA analysis in patients with malignant pleural mesothelioma — S. Emri, H. Akbulut, et al. (2001)
• Flow cytometric analysis of ploidy in immunohistochemically confirmed examples of malignant epithelial mesothelioma — H.F. Frierson, S.E. Mills, et al. (1988)
• Spectrum of peritoneal mesothelioma in childhood: clinical and histopathologic features, including DNA cytometry — F.K. Niggli, T.J. Gray, et al. (1994)
• A predictive assay for human tumor cellular response to hyperthermia using dansyl lysine staining and flow cytometry — S.Y. Woo, G.C. Rice, et al. (1988)
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