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. 2021 Dec;48(12):1455-1462.
doi: 10.1111/cup.14083. Epub 2021 Jul 2.

Diagnosis of melanoma by imaging mass spectrometry: Development and validation of a melanoma prediction model

Rami N Al-Rohil  1 , Jessica L Moore  2 , Nathan Heath Patterson  2   3 , Sarah Nicholson  2 , Nico Verbeeck  4 , Marc Claesen  4 , Jameelah Z Muhammad  2 , Richard M Caprioli  2   3 , Jeremy L Norris  2   3 , Sara Kantrow  5 , Margaret Compton  6 , Jason Robbins  5 , Ahmed K Alomari  7
Affiliations

Diagnosis of melanoma by imaging mass spectrometry: Development and validation of a melanoma prediction model

Rami N Al-Rohil et al. J Cutan Pathol. 2021 Dec.

Abstract

Background: The definitive diagnosis of melanocytic neoplasia using solely histopathologic evaluation can be challenging. Novel techniques that objectively confirm diagnoses are needed. This study details the development and validation of a melanoma prediction model from spatially resolved multivariate protein expression profiles generated by imaging mass spectrometry (IMS).

Methods: Three board-certified dermatopathologists blindly evaluated 333 samples. Samples with triply concordant diagnoses were included in this study, divided into a training set (n = 241) and a test set (n = 92). Both the training and test sets included various representative subclasses of unambiguous nevi and melanomas. A prediction model was developed from the training set using a linear support vector machine classification model.

Results: We validated the prediction model on the independent test set of 92 specimens (75 classified correctly, 2 misclassified, and 15 indeterminate). IMS detects melanoma with a sensitivity of 97.6% and a specificity of 96.4% when evaluating each unique spot. IMS predicts melanoma at the sample level with a sensitivity of 97.3% and a specificity of 97.5%. Indeterminate results were excluded from sensitivity and specificity calculations.

Conclusion: This study provides evidence that IMS-based proteomics results are highly concordant to diagnostic results obtained by careful histopathologic evaluation from a panel of expert dermatopathologists.

Keywords: MALDI IMS; diagnostic test; imaging mass spectrometry; melanoma; proteomics.

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Conflict of interest statement

Conflict of Interest Statement

JLM, NHP, SN, RMC, JLN, and JR disclose a financial interest in Frontier Diagnostics, LLC (FDx). FDx has issued and pending patent applications in the US Patent Office that include part of the methods described in this paper. NV and MC, principals of Aspect Analytics NV, are paid consultants and provide services to FDx.

Figures

Figure 1:
Figure 1:. Study Design.
Three dermatopathologists independently provided a sample diagnosis. The study included only triconcordant samples in the training and test set.
Figure 2:
Figure 2:. Example analysis of melanoma and benign nevus analyzed by IMS.
The samples were H&E stained and scanned using a Huron Tissuescope digital slide scanner with a 20× objective and a 1.5× Barlow lens. Panel A and C show a low magnification image of the entire lesion and a higher magnification of annotated areas of interest for melanoma (B) and nevus (D). Panels E and F show average mass spectra obtained from each sample. The red trace indicates the averaged mass spectrum from all melanoma spots in (A), while the blue trace is the averaged mass spectrum from all benign spots in (C). Panel (F) shows the averaged mass spectra of these regions from m/z 1050–1250. The asterisks denote peaks with relative intensities that differ between nevus and melanoma.
See this image and copyright information in PMC

References

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