Melanoma biomarker expression in melanocytic tumor progression: a tissue microarray study.
BACKGROUND
The elucidation of protein biomarkers that are differentially expressed in human melanocytic tumors during tumor progression may lead to the identification of therapeutic targets and novel diagnostic tests. In a meeting chaired by Dr Mihm, a list of biomarkers of interest in melanoma was compiled. The specialized programs of research excellence (SPORE) in skin cancer developed a melanocytic tumor progression tissue microarray (TMA) to evaluate these candidate biomarkers. In addition to markers reported elsewhere, we evaluated c-Kit, MITF, MART1, HMB-45 and bcl-2.


METHODS
The TMA contains 480 cores of benign nevi, primary cutaneous melanoma and melanoma metastases. Immunohistochemical detection of melanoma biomarkers, including c-Kit, MITF, MART-1, HMB-45 and bcl-2 was performed.


RESULTS
Intense nuclear staining for MITF protein was observed in 83% of nevi, 56% of primary melanomas and 23% of metastases. Bcl-2 expression was reduced with progression to metastasis (detected in 86, 89 and 52% of nevi, primaries and metastases, respectively), contrary to MART-1, which showed no differential expression (74, 85 and 84%). HMB-45 was observed in 18% of nevi and most (72 and 75%) primary melanomas and metastases. c-Kit protein increased with progression from nevi to primary tumor (10 and 77% of cases, respectively) and was decreased in metastases (26% of cases).


CONCLUSIONS
Through a collaboration of the Skin SPOREs sponsored by the Organ Systems Branch of the National Cancer Institute (NCI), we identified a list of melanoma biomarkers of interest, developed a melanocytic tumor progression TMA and completed a coordinated analysis of these biomarkers. This TMA has served as a powerful validation tool for newly identified and known melanoma biomarkers by revealing trends in expression during tumor progression and by confirming the heterogeneity of biomarker expression in cutaneous melanocytic tumors.
Nazarian
Rosalynn M
RM
Dermatopathology Unit, Pathology Service, Massachusetts General Hospital, Boston, MA, USA.
Prieto
Victor G
VG
Elder
David E
DE
Duncan
Lyn M
LM
D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D058965:MART-1 Antigen; D008544:Melanocytes / Q000378:metabolism* / Q000473:pathology; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D058950:Melanoma-Specific Antigens; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D040081:Protein Array Analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D000077022:Survivin
D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D058965:MART-1 Antigen; C497234:MITF protein, human; C548667:MLANA protein, human; D058950:Melanoma-Specific Antigens; D051739:Microphthalmia-Associated Transcription Factor; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D019009:Proto-Oncogene Proteins c-kit