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Heterogeneous expression of melanoma-associated antigens and HLA-A2 in metastatic melanoma in vivo.

Abstract：

:MART-1/MelanA and Pmel17/gp100 are melanoma-associated antigens (MAAs) that can be recognized by tumor-infiltrating lymphocytes (TILs) capable of mediating successful adoptive therapy in vivo. Analysis of melanoma cell lines in vitro has demonstrated that heterogeneous antigen expression in the context of class I MHC is a significant co-factor in determining the recognition of melanoma targets by cytotoxic lymphocytes (CTLs). In this study, 217 specimens from 103 patients with metastatic melanoma were examined for the expression of MART-1/MelanA (monoclonal antibody [MAb] M27C10) and Pmel17/gp100 (HMB45 MAb) by immuno-histochemistry. Marked heterogeneity in the expression of both MAAs was confirmed by analysis of the percentage of positively staining tumor cells or the average intensity of tumor staining. We also noted heterogeneity of expression among multiple lesions taken from different anatomic sites within a patient. A dissociation was noted in the detection of MART-1 and gp100 in some lesions, with gp100 being undetectable in 24% of the lesions and MART-1 being undetectable in 11%. In several cases, loss of one MAA was not associated with loss of the other MAA, suggesting that MART-1 can represent a useful additional marker for the diagnosis of melanoma in gp100 (HMB45)-negative lesions. Of the 217 specimens, 155 were obtained from HLA-A*0201 patients, of which 6% were negative for HLA-A2, 8% were negative for MART-1/MelanA and 21% were negative for Pmel17/gp100. The potential significance of our findings is illustrated by a case study in which a patient with melanoma experienced rapid tumor progression in association with loss of either MAA or HLA expression in several lesions.

journal_name

Int J Cancer

journal_title

International journal of cancer

authors

Cormier JN,Hijazi YM,Abati A,Fetsch P,Bettinotti M,Steinberg SM,Rosenberg SA,Marincola FM

doi

10.1002/(sici)1097-0215(19980209)75:4<517::aid-ijc

subject

Has Abstract

pub_date

1998-02-09 00:00:00

pages

517-24

issue

eissn

0020-7136

issn

1097-0215

pii

10.1002/(SICI)1097-0215(19980209)75:4<517::AID-IJC

journal_volume

pub_type

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Heterogeneous expression of melanoma-associated antigens and HLA-A2 in metastatic melanoma in vivo.