SERPINE1 expression discriminates site-specific metastasis in human melanoma.
Depth of invasion, a quantifier of vertical growth, is a major cutaneous melanoma staging factor. Stromal penetrance requires pericellular proteolysis regulated by the serine protease and matrix metalloproteinase cascades. The serine protease inhibitor SERPINE1, a poor prognosis biomarker in various cancers, promotes tumor progression likely by titrating the extent and local of plasmin-initiated matrix remodelling. SERPINE1 in human melanoma was assessed using tissue arrays that included primary/metastatic tumors and normal skin. SERPINE1 was basal layer-restricted in the normal epidermis. SERPINE1 immunoreactivity was evident in 27/28 primary (96%) and 24/26 metastatic tumors (92%); cutaneous metastases (80%) had significantly elevated SERPINE1 levels compared with low signals characteristic of lymph node lesions. Moderate SERPINE1 expression was a general finding in primary melanoma, whereas reduced or increased SERPINE1 immunolocalization typified metastatic deposits. The amplitude of SERPINE1 expression may impact melanoma site-specific dissemination, with cutaneous metastases representing a high-SERPINE1 tumor subtype.
R Matthew
RM
Klein
Daniel
D
Bernstein
Steven P
SP
Higgins
Craig E
CE
Higgins
Paul J
PJ
Higgins
D014408:Biomarkers, Tumor / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008545:Melanoma / Q000378:metabolism* / Q000556:secondary*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary
D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human