Analysis of expression of the melanoma-associated antigens MART-1 and gp100 in metastatic melanoma cell lines and in in situ lesions

Francesco M. Marincola, Yasmine M. Hijazi, Patricia Fetsch, Michael L. Salgaller, Licia Rivoltini, Janice Cormier, Toni B. Simonis, Paul H. Duray, Meenhard Herlyn, Yutaka Kawakami, Steven A. Rosenberg

Research output: Contribution to journalArticle

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Abstract

MART-1 and gp100 melanoma associated antigens (MAA) are expressed by cells of the melanocytic lineage and are recognized by the majority of HLA- A2 restricted tumor-infiltrating lymphocytes. Heterogeneity of expression of MAA in tumor deposits may affect the natural history or response to therapy of patients with melanoma. In this study, we evaluated the expression of these MAA with a new monoclonal antibody (mAb) directed against MART-1 (M2- 7C10) and the commercially available HMB45 mAb directed against gp100. Expression was tested in vitro by intracellular fluorescence analysis and in vivo by immunophenotyping of tissue specimens. Nine melanoma cell lines and 25 tissue specimens from metastatic melanoma were analyzed. One cell line did not express MART-1 or gp100. The expression of both antigens was more heterogeneous and significantly reduced (p < 0.01) in melanoma cell lines compared with melanocytes, suggesting progressive loss of expression of MAA by neoplastic cells. None of the nonmelanoma cancer lines tested stained for MART-1 or gp100. Analysis of melanoma lesions by immunohistochemistry showed significant heterogeneity of expression of both MART-1 and gp100 MAA either as a percentage of cells expressing MAA or as intensity of expression. Ten of 25 frozen sections expressed MART-1 in <50% of the cells. In 6 of 25 lesions, immunoreactivity for MART-1 was totally absent. Fine needle aspiration of metastatic lesions seemed to yield information accurately about amount and heterogeneity of expression of MAA in tumor lesions in vivo. Heterogeneity of expression of MAA may be one of several mechanisms leading to tumor escape from immune recognition, and pretreatment evaluation of tumor lesion for expression of these antigens may help in selecting patients best suited to antigen-specific vaccine therapies.

Original languageEnglish
Pages (from-to)192-205
Number of pages14
JournalJournal of Immunotherapy
Volume19
Issue number3
DOIs
Publication statusPublished - 1996
Externally publishedYes

Fingerprint

Melanoma-Specific Antigens
Melanoma
Cell Line
gp100 Melanoma Antigen
Antigens
Neoplasms
Monoclonal Antibodies
Tumor Escape
Tumor-Infiltrating Lymphocytes
HLA-A2 Antigen
Active Immunotherapy
Immunophenotyping
Melanocytes
Frozen Sections
Cell Lineage
Fine Needle Biopsy
Natural History
Fluorescence
Immunohistochemistry

Keywords

  • FNA
  • gp100
  • MART-1
  • Melanoma

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Marincola, F. M., Hijazi, Y. M., Fetsch, P., Salgaller, M. L., Rivoltini, L., Cormier, J., ... Rosenberg, S. A. (1996). Analysis of expression of the melanoma-associated antigens MART-1 and gp100 in metastatic melanoma cell lines and in in situ lesions. Journal of Immunotherapy, 19(3), 192-205. https://doi.org/10.1097/00002371-199605000-00004

Analysis of expression of the melanoma-associated antigens MART-1 and gp100 in metastatic melanoma cell lines and in in situ lesions. / Marincola, Francesco M.; Hijazi, Yasmine M.; Fetsch, Patricia; Salgaller, Michael L.; Rivoltini, Licia; Cormier, Janice; Simonis, Toni B.; Duray, Paul H.; Herlyn, Meenhard; Kawakami, Yutaka; Rosenberg, Steven A.

In: Journal of Immunotherapy, Vol. 19, No. 3, 1996, p. 192-205.

Research output: Contribution to journalArticle

Marincola, FM, Hijazi, YM, Fetsch, P, Salgaller, ML, Rivoltini, L, Cormier, J, Simonis, TB, Duray, PH, Herlyn, M, Kawakami, Y & Rosenberg, SA 1996, 'Analysis of expression of the melanoma-associated antigens MART-1 and gp100 in metastatic melanoma cell lines and in in situ lesions', Journal of Immunotherapy, vol. 19, no. 3, pp. 192-205. https://doi.org/10.1097/00002371-199605000-00004
Marincola, Francesco M. ; Hijazi, Yasmine M. ; Fetsch, Patricia ; Salgaller, Michael L. ; Rivoltini, Licia ; Cormier, Janice ; Simonis, Toni B. ; Duray, Paul H. ; Herlyn, Meenhard ; Kawakami, Yutaka ; Rosenberg, Steven A. / Analysis of expression of the melanoma-associated antigens MART-1 and gp100 in metastatic melanoma cell lines and in in situ lesions. In: Journal of Immunotherapy. 1996 ; Vol. 19, No. 3. pp. 192-205.
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abstract = "MART-1 and gp100 melanoma associated antigens (MAA) are expressed by cells of the melanocytic lineage and are recognized by the majority of HLA- A2 restricted tumor-infiltrating lymphocytes. Heterogeneity of expression of MAA in tumor deposits may affect the natural history or response to therapy of patients with melanoma. In this study, we evaluated the expression of these MAA with a new monoclonal antibody (mAb) directed against MART-1 (M2- 7C10) and the commercially available HMB45 mAb directed against gp100. Expression was tested in vitro by intracellular fluorescence analysis and in vivo by immunophenotyping of tissue specimens. Nine melanoma cell lines and 25 tissue specimens from metastatic melanoma were analyzed. One cell line did not express MART-1 or gp100. The expression of both antigens was more heterogeneous and significantly reduced (p < 0.01) in melanoma cell lines compared with melanocytes, suggesting progressive loss of expression of MAA by neoplastic cells. None of the nonmelanoma cancer lines tested stained for MART-1 or gp100. Analysis of melanoma lesions by immunohistochemistry showed significant heterogeneity of expression of both MART-1 and gp100 MAA either as a percentage of cells expressing MAA or as intensity of expression. Ten of 25 frozen sections expressed MART-1 in <50{\%} of the cells. In 6 of 25 lesions, immunoreactivity for MART-1 was totally absent. Fine needle aspiration of metastatic lesions seemed to yield information accurately about amount and heterogeneity of expression of MAA in tumor lesions in vivo. Heterogeneity of expression of MAA may be one of several mechanisms leading to tumor escape from immune recognition, and pretreatment evaluation of tumor lesion for expression of these antigens may help in selecting patients best suited to antigen-specific vaccine therapies.",
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AU - Cormier, Janice

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AU - Kawakami, Yutaka

AU - Rosenberg, Steven A.

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