Imaging Mass Spectrometry—A New and Promising Method to Differentiate Spitz Nevi From Spitzoid Malignant Melanomas

Department of Dermatology, Yale University School of Medicine and the Yale Cancer Center, New Haven, CT 06520, USA.
The American Journal of dermatopathology (Impact Factor: 1.39). 12/2011; 34(1):82-90. DOI: 10.1097/DAD.0b013e31823df1e2
Source: PubMed


Differentiating Spitz nevus (SN) from Spitzoid malignant melanoma (SMM) is one the most difficult problems in dermatopathology. SPECIFIC AIM: To identify differences on proteomic level between SN and SMM.
We performed Imaging Mass Spectrometry analysis on formalin-fixed, paraffin-embedded tissue samples to identify differences on proteomic level between SN and SMM. The diagnosis of SN and SMM was based on histopathologic criteria, clinical features, and follow-up data, which confirmed that none of the lesions diagnosed as SN recurred or metastasized. The melanocytic component (tumor) and tumor microenvironment (dermis) from 114 cases of SN and SMM from the Yale Spitzoid Neoplasm Repository were analyzed. After obtaining mass spectra from each sample, classification models were built using a training set of biopsies from 26 SN and 25 SMM separately for tumor and for dermis. The classification algorithms developed on the training data set were validated on another set of 30 samples from SN and 33 from SMM.
We found proteomic differences between the melanocytic components of SN and SMM and identified 5 peptides that were differentially expressed in the 2 groups. From these data, 29 of 30 SN and 26 of 29 SMM were recognized correctly based on tumor analysis in the validation set. This method correctly classified SN with 97% sensitivity and 90% specificity in the validation cohort.
Imaging Mass Spectrometry analysis can reliably differentiate SN from SMM in formalin-fixed, paraffin-embedded tissue based on proteomic differences.

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    • "MALDI- MSI studies on the clinical status and as risk assessments with respect to disease developments, e.g., cancer states of tumor genesis (Fehniger et al. 2011), and drug responders, as well as long-term survival (Marko-Varga et al. 2012; Sugihara et al. 2014). In addition to our own melanoma studies, studies undertaken by Caprioli et al., was first to present MALDI-MSI data where they used metastatic tumors, identifying calcyclin (Hardesty and Caprioli 2008; Lazova et al. 2012). At the Center of Excellence in Lund (http://www. "
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    • "Subjects with low m/z 6079 levels showed significantly higher survival rates than patients expressing high levels of m/z 6079 [35]. In a follow-up study, the Caprioli group applied MALDI-MSI to differentiate and classify resected benign and malignant Spitz nevi and compared the molecular profiles of the biopsy sample to histological indices that provided the diagnostic standard for the presence of a tumor [36]. The differential expression of five peptides could be used to separate tumor bearing from nontumor bearing samples with 97% sensitivity and 90% specificity. "
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    • "MALDI-MSI of FFPE tissues was also used to distinguish spitz nevus from spitzoid malignant melanoma. Five peptides were found to be differentially expressed and could classify spitz nevus with 97 % sensitivity and 90 % specificity using a validation cohort of 59 samples (Lazova et al. 2012). "
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