MASS SPECTROMETRY IMAGING OF BENIGN MELANOCYTIC NEVI AND MALIGNANT MELANOMAS

1 . A method for differentiating benign melanocytic nevi from malignant melanomas, the method comprising:

(a) subjecting a skin lesion sample from a patient to mass spectrometry;

(b) obtaining a mass spectrometry profile from the skin lesion sample;

(c) comparing the mass spectrometry profile of the skin lesion sample to a reference profile, wherein the reference profile includes a statistical average profile from a plurality of known normal, benign melanocytic nevi, and/or a plurality of known malignant melanoma; and

(d) classifying the skin lesion sample as a benign melanocytic nevus or a melanocytic malignant melanoma based on a level of similarity between the mass spectrometry profile of the skin lesion sample and the reference profile.

2 . The method of claim 1 , wherein the statistical average profile is generated using a genetic algorithm which defines one or more markers.

3 . The method of claim 1 , wherein the statistical average profile is generated using a genetic algorithm which defines six or more markers.

4 . The method of claim 2 , wherein the statistical average profile comprises markers represented by peptide peaks at one or more of m/z 683.47±0.2, m/z 738.45±0.2, m/z 960.57±0.2, m/z 983.61±0.2, m/z 1043.70±0.2, m/z 1110.64±0.2, m/z 1143.63±0.2, m/z 1215.71±0.2, m/z 1254.73±0.2, m/z 1314.76±0.2, m/z 1454.86±0.2, m/z 1473.84±0.2, m/z 1489.94±0.2, m/z 1505.94±0.2, m/z 1507.90±0.2, m/z 1513.83±0.2, m/z 1519.97±0.2, m/z 1521.76±0.2, m/z 1569.89±0.2, m/z 1592.92±0.2, m/z 1633.91±0.2, m/z 1730.88±0.2, m/z 1878.02±0.2, and m/z 2187.17±0.2.

5 . The method of claim 1 , wherein the statistical average profile is generated using a linear determinant analysis on a total spectrum from the plurality of known normal, benign melanocytic nevi, and/or the plurality of known malignant melanoma.

6 . The method of claim 5 , wherein the linear discriminant analysis shows a sensitivity and a specificity of at least 95% in correctly classifying the skin lesion sample.

7 . The method of claim 1 , wherein the method has a sensitivity and a specificity of at least 95% in correctly classifying the skin lesion sample.

8 . The method of claim 1 , wherein the mass spectrometry is matrix assisted laser desorption mass spectrometry.

9 . The method of claim 1 , comprising repeating the steps of (a)-(d) on the skin lesion sample.

10 . The method of claim 1 , wherein the skin lesion sample comprises melanocytic components.

11 . The method of claim 1 , wherein the skin lesion sample comprises stromal components and/or benign melanocytic nevi components.

12 . The method of claim 1 , wherein both melanocytic and stromal components of the skin lesion sample are subjected to mass spectrometry.

13 . The method of claim 1 , comprising treating the patient with at least one of chemotherapy, immunotherapy, toxin therapy, surgery, and radiotherapy when the patient is identified as having malignant melanoma.

14 . The method of claim 1 , comprising performing histologic analysis on the skin lesion sample.

15 . The method of claim 1 , wherein the plurality of known normal, benign melanocytic nevi, and the plurality of known malignant melanoma are classified by immunohistochemical analysis, genetic analysis, patient outcome, or a combination thereof.

16 . The method of claim 1 , comprising immunohistochemical analysis on the skin lesion sample.

17 . A method for differentiating benign melanocytic nevi from malignant melanomas, the method comprising:

(a) subjecting a skin lesion sample from a patient to mass spectrometry;

(b) obtaining a mass spectrometry profile from the skin lesion sample;

(c) comparing the mass spectrometry profile of the skin lesion sample to a reference profile, wherein the reference profile includes a statistical average profile from a plurality of known normal, benign melanocytic nevi, and/or a plurality of known malignant melanoma; and

(d) classifying the skin lesion sample as a benign melanocytic nevus or a malignant melanoma based on a level of similarity between the mass spectrometry profile of the skin lesion sample and the reference profile,

wherein the statistical average profile is generated using a linear determinant analysis on a total spectrum from the plurality of known normal, benign melanocytic nevi, and/or the plurality of known malignant melanoma, and

wherein the linear discriminant analysis shows a sensitivity and a specificity of at least 95% in correctly classifying the skin lesion sample.

18 . The method of claim 17 , wherein the sensitivity and specificity is at least 97% in correctly classifying the skin lesion sample.

19 . A method for differentiating benign melanocytic nevi from malignant melanomas, the method comprising:

(a) subjecting a skin lesion sample from a patient to mass spectrometry;

(b) obtaining a mass spectrometry profile from the skin lesion sample;

(c) comparing the mass spectrometry profile of the skin lesion sample to a reference profile, wherein the reference profile includes a statistical average profile from a plurality of known normal, benign melanocytic nevi, and/or a plurality of known malignant melanoma; and

(d) classifying the skin lesion sample as a benign melanocytic nevus or a melanocytic malignant melanoma based on a level of similarity between the mass spectrometry profile of the skin lesion sample and the reference profile,

wherein the statistical average profile is generated using a genetic algorithm which defines one or more markers.

20 . The method of claim 19 , the statistical average profile comprises markers represented by peptide peaks at one or more of m/z 683.47±0.2, m/z 738.45±0.2, m/z 960.57±0.2, m/z 983.61±0.2, m/z 1043.70±0.2, m/z 1110.64±0.2, m/z 1143.63±0.2, m/z 1215.71±0.2, m/z 1254.73±0.2, m/z 1314.76±0.2, m/z 1454.86±0.2, m/z 1473.84±0.2, m/z 1489.94±0.2, m/z 1505.94±0.2, m/z 1507.90±0.2, m/z 1513.83±0.2, m/z 1519.97±0.2, m/z 1521.76±0.2, m/z 1569.89±0.2, m/z 1592.92±0.2, m/z 1633.91±0.2, m/z 1730.88±0.2, m/z 1878.02±0.2, and m/z 2187.17±0.2.