Melanophages reside in hypermelanotic, aberrantly glycosylated tumor areas and predict improved outcome in primary cutaneous malignant melanoma.
BACKGROUND
Previously, hypermelanotic regions of cutaneous malignant melanoma (CMM) were found to contain a mixture of highly melanized melanoma cells and melanophages. Both cell types produced beta1,6-branched oligosaccharides. These sugars are used for motility by myeloid cells and cancer cells alike and are associated with poor survival in carcinomas of the breast, colon and lung. This study further investigated associations between melanophages and beta1,6-branched oligosaccharides and their potential contributions to patient outcome.


METHODS
Individual archival melanomas and high-throughput melanoma tissue microarrays were stained for melanophages with azure blue/S100 and for beta1,6-branched oligosaccharides with the lectin leukocytic phytohemagglutinin (LPHA, a selective marker for beta1,6-branched oligosaccharides).


RESULTS
In primary CMM, melanophages were highly enriched in hypermelanotic, LPHA-positive tumor regions and correlated with improved outcome at 10- and 20-year follow ups. While the combination of melanophages, LPHA positivity and high pigmentation indicated better outcome, a subset of LPHA-positive cells not associated with melanophages indicated worse outcome.


CONCLUSIONS
This is the first report of an anti-tumor role for the melanophage in melanoma biology. There appeared to be two classes of beta1,6-branched oligosaccharide-producing melanoma cells with opposing effects on outcome: one that attracted melanophages (better) and another that did not (worse). The findings disclose new aspects of the immune system and aberrant glycosylation in CMM.
Handerson
Tamara
T
Department of Pathology, Greenwich Hospital, CT, USA.
Berger
Aaron
A
Harigopol
Malini
M
Rimm
David
D
Nishigori
Chikako
C
Ueda
Masato
M
Miyoshi
Eiji
E
Taniguchi
Naoyuki
N
Pawelek
John
J
D014408:Biomarkers, Tumor / Q000378:metabolism; D006031:Glycosylation; D006644:Histiocytes / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology*; D008545:Melanoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D025942:Oligosaccharides, Branched-Chain / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D008543:Melanins; D025942:Oligosaccharides, Branched-Chain