Method for differentiating spitz nevi from spitzoid malignant melanoma
The present invention provides for a mass spectrometry proteomic approach to distinguishing Spitz nevi from Spitzoid malignant melanoma. Histology directed mass spectral profiling allows for targeted analysis of sites of melanocytic lesion within formalin-fixed, paraffin embedded excisional biopsies. The classification system identified 5 peptide peaks, of which two have been identified as originating from vimentin and actin. A sensitivity and specificity for Spitz nevi of 97% and 90%, respectively, were achieved.
1. A method of differentiating Spitz nevi from Spitzoid malignant melanoma comprising:
(a) subjecting a skin lesion sample from a patient to mass spectrometry;
(b) obtaining a mass spectrometric protein profile from said sample;
(c) comparing said mass spectrometric protein profile to a known normal, Spitz nevi and/or Spitzoid malignant melanoma profile; and
(d) classifying said lesion as a Spitz nevi or Spitzoid malignant melanoma based on the similarities and differences between said mass spectrometric protein profile and said known profile or profiles.
2. The method of claim 1 , wherein said mass spectrometry is secondary ion mass spectrometry, laser desorption mass spectrometry, matrix assisted laser desorption mass spectrometry, electrospray mass spectrometry, or desorption electrospray ionization.
3. The method of claim 1 , further comprising obtaining said sample from said patient.
4. The method of claim 1 , further comprising making a treatment decision for said patient.
5. The method of claim 1 , wherein said patient is identified as having Spitz nevi, then further comprising repeating steps (a)-(d) on said lesion in 6-12 months, 6-18 months, 6-24 months, 12-18 months, 12-24 months or 18-24 months.
6. The method of claim 1 , wherein said patient is identified as having Spitzoid malignant melanoma, then further comprising treating said patient with chemotherapy, immunotherapy, toxin therapy or radiotherapy.
7. The method of claim 1 , further comprising assessing one or more patient history parameters from said patient.
8. The method of claim 1 , further comprising performing a mass spectrometric analysis of a known Spitz nevi and/or Spitzoid malignant melanoma lesion.
9. The method of claim 1 , further comprising performing histologic analysis on said sample.
10. The method of claim 1 , further comprising making a prediction of said patient's survival based on said classification.
11. The method of claim 1 , wherein the skin lesion sample consists essentially of melanocytic components.
12. The method of claim 1 , wherein the mass spectrometric profile comprises markers of vimentin and actin.
13. The method of claim 11 , wherein the mass spectrometric profile comprises peptide peaks at m/z 976.5±0.2, m/z 1060.2±0.2, m/z 1410.7±0.2, m/z 1336.7±0.2 and m/z 1428.8±0.2 are examined.
14. The method of claim 1 , wherein the skin lesion sample consists essentially of stromal components.
15. The method of claim 14 , wherein the mass spectrometric profile comprises peptide peaks at m/z 713.2±0.2, m/z 1251.8±0.2, m/z 1287.7±0.2, m/z 1365.8±0.2, m/z 1428.8±0.2, m/z 1685.9±0.2, m/z 2519.3±0.2, m/z 2632.3±0.2, m/z 2773.3±0.2, m/z 3224.5±0.2, m/z 3287.1±0.2 and m/z 3411.8±0.2 are examined.
16. The method of claim 1 , wherein both melanocytic and stromal components of said skin lesion sample are examined.
17. The method of claim 1 , wherein said patient has previously had immunohistochemical analysis of said lesion.
18. The method of claim 17 , wherein said previous immunohistochemical analysis in inidicated that said lesion was a Spitz nevus.
19. The method of claim 17 , wherein said previous immunohistochemical analysis in inidicated that said lesion was a Spitzoid malignant melanoma.
20. The method of claim 1 , further comprising immunohistochemical analysis on said skin lesion sample.