Immunoreactivity with the Anti-MAGE Antibody 57B in Malignant Melanoma: Frequency of Expression and Correlation with Prognostic Parameters

Busam, Klaus J.; Iversen, Kristin; Berwick, Marianne; Spagnoli, G.C.; Old, Lloyd J.; Jungbluth, Achim A.

doi:10.1038/modpathol.3880078

Cited by 38 publications

(39 citation statements)

References 37 publications

(42 reference statements)

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“…Our findings are more in keeping with those of Brasseur et al (38), who reported MAGE-A1 in 48% of metastases and 16% of primary melanomas, although that study was based on reverse transcription-PCR analysis. Previous studies did not find a difference in expression of MAGE-A4 between primary and metastatic melanomas, and no correlation with stage or thickness could be established (39), although a correlation could be seen with the presence of an inflammatory infiltrate. However, the study consisted of fewer cases, and tumor and metastatic lesion were not derived from the same patients (39).…”

Section: Discussionmentioning

confidence: 85%

“…Previous studies did not find a difference in expression of MAGE-A4 between primary and metastatic melanomas, and no correlation with stage or thickness could be established (39), although a correlation could be seen with the presence of an inflammatory infiltrate. However, the study consisted of fewer cases, and tumor and metastatic lesion were not derived from the same patients (39). Likewise, few studies have looked at patterns of NY-ESO-1 expression in melanoma, although one smaller study did find NY-ESO-1 mRNA expression to be increased in metastases compared with primary samples (32).…”

Section: Discussionmentioning

confidence: 85%

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Tumor Antigen Expression in Melanoma Varies According to Antigen and Stage

Barrow

Browning

MacGregor

et al. 2006

Clinical Cancer Research

215

194

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Purpose: Melanoma cells express antigens that can induce T-cell and antibody responses.Obtaining a detailed understanding of antigen expression in primary and metastatic melanoma is essential if these molecules are to be useful targets for immunotherapy of melanoma. Experimental Design: Malignant melanomas (n = 586) from 426 patients were typed for antigen expression. Multiple samples were available from 86 individuals, enabling analysis of antigen expression patterns over time. Paraffin-embedded samples were tested by immunohistochemistry for the presence of the differentiation antigens: gp100, Melan-A, tyrosinase, and the ''cancer/testis'' antigens MAGE-A1, MAGE-A4, and NY-ESO-1. Results: Samples were primary tumors (n = 251), lymph node metastases (n = 174), s.c. metastases (n = 71), and distant metastases (n = 90). The differentiation antigens were strongly expressed in 93% to 95% of tumors regardless of stage. In contrast, the frequency of cancer/ testis antigen expression in primary tumors for MAGE-A1, MAGE-A4, and NY-ESO-1 was lower (20%, 9%, and 45%, respectively). MAGE-A1 and MAGE-A4 were acquired with advancing disease (to 51% and 44% in distant metastases, respectively) but not NY-ESO-1, which remained positive in 45%. MAGE-A1 expression was twice as prevalent in ulcerated primaries as in nonulcerated primaries (30% versus 15%; P = 0.006) and in thicker as opposed to thin melanomas (26% versus 10%; P = 0.1). Conclusions: This large series describes patterns of antigen expression in melanoma and their evolution over time. This will help inform decisions about selection of patients and target antigens for melanoma immunotherapy clinical trials.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 85%

Tumor Antigen Expression in Melanoma Varies According to Antigen and Stage

Barrow

Browning

MacGregor

et al. 2006

Clinical Cancer Research

215

194

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“…In malignant melanoma, MAGE protein expression analyzed immunohistochemically with mAb 57B has been shown to correlate only with lymphocytic infiltrates, while no correlation was found with any other prognostic parameter. 47 On an mRNA level, correlation between CT antigen expression and tumor stage has been reported in several tumors such as renal cell carcinoma, 48 bladder 49 and esophageal carcinoma, 50 and melanoma. 51 This association has not been demonstrated in others: head and neck carcinoma, 52 seminoma 18 stomach, 53 or colon.…”

Section: Discussionmentioning

confidence: 99%

Expression of cancer–testis antigens in endometrial carcinomas using a tissue microarray

et al. 2005

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Cancer-testis (CT) antigens are expressed in a variety of malignant tumors, but in normal adult tissue, they are only expressed in testicular germ cells. Owing to this tumor-associated expression pattern, these antigens are of major interest as potential targets for immunotherapy and possibly for diagnostic purposes. This study was performed to analyze the expression of four CT antigens, NY-ESO-1, MAGE-A3, MAGE-A4, and CT7/MAGE-C1, in endometrial carcinoma using immunohistochemistry, and to correlate expression with histologic subtypes, grade, and expression of WT1 and p53. Formalin-fixed paraffin-embedded tissues of 130 endometrial carcinomas of the following types and grades were analyzed using a tissue microarray: 85 endometrioid carcinomas (FIGO grade 1, 39; grade 2, 11; and grade 3, 35), 18 papillary serous carcinomas, 12 clear cell carcinomas, 13 malignant mixed mullerian tumors, one mucinous adenocarcinoma, and one undifferentiated carcinoma. The following anti-CT monoclonal antibodies/antigens were studied by immunohistochemistry: monoclonal antibody ES121/NY-ESO-1, monoclonal antibody M3H67/MAGE-A3, monoclonal antibody 57B/ MAGE-A4, and monoclonal antibody CT7-33/CT7. The CT expression data were compared to WT1 and p53 protein expression as analyzed in a previous study. Positive staining with anti-CT monoclonal antibodies was graded as follows: focal, o5% positive cells; 1 þ , 5-25% cells; 2 þ , 26-50% cells; 3 þ , 51-75%; and 4 þ , 475% cells. The 3 þ and 4 þ staining patterns were considered homogeneous patterns of potential clinical significance and were scored positive for statistical analysis. In low-grade tumors, the most immunoreactivity was seen with mAb M3H67 but little labeling was observed with the other monoclonal antibodies. In high-grade tumors, monoclonal antibodies M3H67 (25%), 57B (23%), and CT7-33 (20%) showed the highest reactivity, while ES121 showed the lowest immunoreactivity (6%). The staining pattern was mostly heterogeneous. Statistical significance was found solely for the correlation of monoclonal antibody 57B staining and p53 expression. No correlation was found for any anti-CT monoclonal antibody staining and clinical stage or for anti-CT staining and WT1 expression. CT antigens CT7, MAGE-A3 and MAGE-A4, but not NY-ESO-1, are expressed in high-grade endometrial carcinomas, and expression of MAGE-A4 is correlated with the presence of overexpressed p53.

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“…Furthermore, melanocyte-specific antigens expression is of diagnostic value in some soft tissue lesions such as clear cell sarcoma, angiomyolipoma, and lymphangiomyomatosis (2). The increasing number of monoclonal antibodies (Mab) directed against formalin resistant melanoma associated antigens such as gp100 (HMB-45 Mab), Melan A (A103 Mab), CD63 (NKI/C-3 Mab), MAGE 1, MAGE 3, or tyrosinase (T311 Mab) has provided useful diagnostic tools (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). However, some melanocytic lesions lack most of these antigens, and non-melanocytic lesions may express melanocyte-related antigens (17)(18)(19).…”

mentioning

confidence: 99%

PNL2, a New Monoclonal Antibody Directed against a Fixative-Resistant Melanocyte Antigen

et al. 2003

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We report the production of a new monoclonal antibody, PNL2, directed against a fixative resistant melanocyte antigen. The analysis of PNL2 immunostaining on a broad range of normal or malignant human tissues and on various melanocytic lesions revealed its high specificity. PNL2 gave a strong cytoplasmic staining of skin and oral mucosae melanocytes, and staining of granulocytes when used at high concentration. PNL2 stained all intraepidermal nevi irrespective of their histologic type, but common intradermal nevi and the dermal component of compound nevi were largely non-reactive as only scattered nevus cells in the papillary dermis were labeled. PNL2 labeled more than 70% of the neoplastic cells in all primary melanomas irrespective of their histologic type. However, PNL2 did not label desmoplastic melanomas. All metastatic melanomas were also stained but the percentage of labeled cells was occasionally lower than the primary tumor. PNL2, as anti-Melan A and HMB-45 antibodies, stained most of the clear cell sarcoma cells, and a few cells in angiomyolipomas and lymphangioleiomyomatosis. None of the other nonmelanocytic lesions tested were labeled. Proteomic approaches showed that the immunoaffinity purified PNL2-binding complexes isolated from melanoma cell lines comprise at least TAP1, Clathrin 17 and prealbumin proteins, but not the gp100 recognized by HMB-45. In conclusion, this new monoclonal antibody, PNL2, is directed against a new fixative resistant melanocyte associated antigen. This antigen is chemically resistant and thus allows immunostaining after melanin bleaching or decalcification. We also demonstrate that it is different from Melan A and from gp100, even if PNL2 and HMB-45 staining patterns are sometimes similar.

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Immunoreactivity with the Anti-MAGE Antibody 57B in Malignant Melanoma: Frequency of Expression and Correlation with Prognostic Parameters

Cited by 38 publications

References 37 publications

Tumor Antigen Expression in Melanoma Varies According to Antigen and Stage

Tumor Antigen Expression in Melanoma Varies According to Antigen and Stage

Expression of cancer–testis antigens in endometrial carcinomas using a tissue microarray

PNL2, a New Monoclonal Antibody Directed against a Fixative-Resistant Melanocyte Antigen

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