TAP1 down-regulation in primary melanoma lesions: an independent marker of poor prognosis.
Melanoma tumor thickness is a major prognostic factor. Thin lesions, however, may metastasize, and sometimes thick tumors may not. To investigate the role of HLA class I-mediated antigen presentation, we correlated the expression of components of the antigen-processing machinery in primary melanoma lesions with their thickness and with the development of metastases. Seventeen formalin-fixed, paraffin-embedded primary melanomas thinner than 0.76 mm and 21 thicker than 1.50 mm were stained with anti-LMP2, -LMP7, -TAP1, -TAP2, -HLA class I and -beta2-microglobulin monoclonal antibodies. Twenty patients remained tumor-free in the follow-up period (10.5 +/- 1.8 years). Eighteen patients relapsed within a median period of 15.0 months following tumor excision. Expression of all markers in the tested lesions was down-regulated, the frequency ranging from about 40% for LMP and TAP subunits to about 70% for HLA class I antigens. Expression of all markers was not correlated with tumor thickness. Only TAP1 and TAP2 down-regulation was significantly (p = 0.026 and 0.042, respectively) correlated with the development of metastases. This correlation was independent of tumor thickness for TAP1. We suggest that TAP1 and probably TAP2 expression in primary lesions represents an independent prognostic marker in melanoma. Abnormalities in antigen presentation may account for the lack of absolute correlation between tumor thickness and prognosis.
Department of Dermatology, University Hospital, Zurich, Switzerland.
J
J
Kamarashev
S
S
Ferrone
B
B
Seifert
R
R
Böni
F O
FO
Nestle
G
G
Burg
R
R
Dummer
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D026905:Amino Acid Transport Systems; D000911:Antibodies, Monoclonal / Q000378:metabolism; D003546:Cysteine Endopeptidases; D018450:Disease Progression; D018572:Disease-Free Survival; D015536:Down-Regulation; D005095:Exoribonucleases / Q000096:biosynthesis*; D005260:Female; D005500:Follow-Up Studies; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009097:Multienzyme Complexes; D009362:Neoplasm Metastasis; D011379:Prognosis; D046988:Proteasome Endopeptidase Complex; D014176:Protein Biosynthesis; D012008:Recurrence; D029701:Saccharomyces cerevisiae Proteins; D013997:Time Factors; D014763:Viral Matrix Proteins / Q000096:biosynthesis; D001613:beta 2-Microglobulin / Q000096:biosynthesis
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D026905:Amino Acid Transport Systems; D000911:Antibodies, Monoclonal; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D029701:Saccharomyces cerevisiae Proteins; C429825:TAT2 protein, S cerevisiae; D014763:Viral Matrix Proteins; D001613:beta 2-Microglobulin; C071692:TAP2 protein, human; D005095:Exoribonucleases; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex