Immuno-expression of human melanoma stem cell markers in tissues at different stages of the disease.
BACKGROUND
Human cutaneous melanoma can be one of the most aggressive tumors and is extremely resistant to all current therapeutic modalities. Immunohistochemistry (IHC) studies were undertaken to assess independent relative frequency on preferential overexpression and simultaneous expression of four stem cell markers; CD133+, ABCB5+, CD166, and Nestin, at different stages of the disease.


METHODS
Five-micron sections from paraffin blocks from primary melanoma, lymph node (LN) metastases, distant metastases, benign nevi from non-melanoma patients (NMP), and patients with past history of melanoma (MP) were IHC stained with monoclonal antibodies (mAb) to the four stem cell markers.


RESULTS
Overexpression of CD133+ was noted in tissues from LN and distant metastases compared to benign nevi (P < 0.0022, P < 0.013, respectively). Overexpression of ABCB5+ was observed comparing primary melanoma, LN, and distant metastases to benign nevi from NMP (P < 0.0063, P < 0.001, P < 0.00058, respectively). Significant overexpression of ABCB5+ was noted in tissues from LN and distant metastases compared with benign nevi from MP (P < 0.0003, P < 0.0068). None of the benign nevi of NMP demonstrated ABCB5+.


CONCLUSIONS
This study clearly shows the existence of a distinct hyperpolarized population of stem cells and may implicate genetic factors in human cutaneous melanoma. Simultaneous overexpression of CD133+ and Nestin could reflect on their origin or lineage association with a neural stem cell. These findings may open new perspectives for therapeutic implication of a melanoma stem cell in specific cancer therapy.
Sharma
Bhuvnesh K
BK
Maryland Melanoma Center, Franklin Square Hospital Center, Baltimore, Maryland, USA.
Manglik
Vinod
V
Elias
E George
EG
D000071916:AC133 Antigen; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018450:Disease Progression; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D010455:Peptides / Q000378:metabolism; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology
C480744:ABCB5 protein, human; D000071916:AC133 Antigen; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; C000606023:PROM1 protein, human; D010455:Peptides