Validation of tissue microarray technology in malignant pleural mesothelioma

Our plain-English summary of Validation of tissue microarray technology in malignant pleural mesothelioma, by S.C. Kao, K. Lee, N.J. Armstrong, et al (Pathology, 2011).

The study

• Authors: S.C. Kao, K. Lee, N.J. Armstrong, S. Clarke, J. Vardy, N. van Zandwijk, G. Reid, J. Burn, B.C. McCaughan, D.W. Henderson, S. Klebe
• Journal: Pathology
• Published: 2011;43(2):128-32
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aims: Tissue microarray (TMA) technology has been utilised for assessment of cancers including malignant pleural mesothelioma (MPM). Given the intralesional heterogeneity of MPM, it is questionable if TMAs can adequately represent MPMs. We here investigate the validity of TMAs for MPM.

Methods: TMAs were constructed from at least five cores for each of 80 archival tumours processed by two centres between 1994 and 2009. The percentage of cases correctly subtyped on TMAs compared with whole sections, in relation to the number of cores analysed, was calculated. Immunohistochemical labelling for calretinin and D2-40 was performed on TMAs and whole sections. To evaluate the validity of quantitative immunohistochemistry, percentages of positive cells were recorded and two-way analysis of variance (ANOVA) performed.

Results: Five cores were assessable for 91% of patients. Four cores were sufficient to reach concordance with the whole-section result in 98% of cases for calretinin and 99% for D2-40. The correlation of the quantitative scores between the whole section and TMA cores was statistically significant (D2-40, rho = 0.84, p < 2.2e-16; calretinin, rho = 0.65, p = 7.9e-11). Neither the origin nor age of the blocks affected the results.

Conclusion: If a minimum of four cores is used, TMA is an appropriate method for immunohistochemistry in MPM.

In plain English

This laboratory study tested tissue microarrays, a method that places several small tissue cores (here 1 mm wide) from each tumour on one slide. The authors used archived tumour samples from 80 patients with malignant pleural mesothelioma who had extrapleural pneumonectomy at two Sydney hospitals between 1994 and 2009, and compared the cores with whole tissue sections. The study did not examine asbestos exposure. Five or more cores could be assessed in 91% of cases (64 with five, nine with six). With four cores, the microarray matched the whole-section result for the marker calretinin in 98% of cases and for the marker D2-40 in 99%. The percentages of labelled cells on cores and on whole sections were strongly correlated (rho 0.84 for D2-40, 0.65 for calretinin). Scores did not differ significantly between the two hospitals, which fixed tissue differently, or between older and newer samples. The cores could not accurately show the tumour's histological subtype. The authors concluded that, except for subtype, microarrays appear to represent a tumour's immunohistochemical profile adequately if at least four cores are sampled per patient.

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 validation study of tissue microarray technology on a retrospective series of archived tumour samples
• Who was studied: Archived tumour blocks from 80 malignant pleural mesothelioma patients who underwent extrapleural pneumonectomy at Royal Prince Alfred Hospital or Strathfield Private Hospital (Sydney, Australia) between 1994 and 2009. Of these, 61 were epithelioid and 19 biphasic on whole sections.
• Exposure: Asbestos exposure was not studied. The study compared 1 mm tissue microarray cores with whole tumour sections, using immunohistochemical labelling for calretinin and D2-40.
• Main results:
  • Of the 80 cases, 64 had five assessable cores (80%) and nine had six (11%). One case yielded no assessable tumour on the microarray.
  • With four cores, the microarray correctly classified calretinin labelling (positive versus negative, compared with the whole section) in 98% of cases and D2-40 labelling in 99% of cases.
  • The percentages of labelled cells on whole sections and the averages of the cores were statistically significantly and strongly positively correlated: rho 0.84 (p less than 2.2e-16) for D2-40 and rho 0.65 (p = 7.9e-11) for calretinin.
  • For both markers, quantitative scores did not differ significantly between the two hospitals, which used different fixation protocols.
  • Agreement between cores from the same patient: the intraclass correlation was 0.786 (95% CI 0.715 to 0.848) for calretinin (69 patients) and 0.873 (95% CI 0.828 to 0.911) for D2-40 (73 patients).
  • Histological subtype could not be accurately assessed from the 1 mm cores.
• The authors' conclusion: The authors concluded that, except for histological subtype, tissue microarrays appear to adequately represent a mesothelioma's immunohistochemical profile, both diagnostic labelling and quantitative scores, provided at least four cores are sampled per patient.
• Limitations the authors state:
  • Tumour areas were marked on the original slides, but after further tissue handling and deeper cutting the tumour surface in some blocks was different, which the authors say probably contributed to discrepant subtype findings.
  • The total number of tissue blocks per specimen had not been recorded for all cases (available for 66 cases).
  • Quantitative scoring used only the percentage of labelled cells and did not take labelling intensity into account, which the authors considered too subjective.

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, Calretinin, Podoplanin (D2-40), Immunohistochemistry.

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