Expression of melan‐a/MART‐1 antigen as a prognostic factor in primary cutaneous melanoma

Berset, Magali; Cerottini, Jean‐Philippe; Guggisberg, D.; Romero, Pedro; Burri, Françoise; Rimoldi, Donata; Panizzon, Renato G.

doi:10.1002/1097-0215(20010120)95:1<73::aid-ijc1013>3.3.co;2-j

Cited by 8 publications

(14 citation statements)

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“…Tumor-infiltrating lymphocytes (TIL) have been used in these cell transfer therapies and have been shown to recognize a variety of melanoma TAA (Kawakami et al, 2000(Kawakami et al, , 2001Harada et al, 2001;Huang et al, 2004). In melanoma, the most commonly recognized TAA is the MART-1, melanoma melanocyte differentiation antigen, which is expressed in approximately 90% of melanomas (Cormier et al, 1998;Berset et al, 2001). In a recent trial of adoptive immunotherapy after nonmyeloablative lymphodepleting chemotherapy, 46% of patients with metastatic melanoma exhibited an objective regression (Dudley et al, 2002a).…”

Section: Introductionmentioning

confidence: 99%

Transfer of a TCR Gene Derived from a Patient with a Marked Antitumor Response Conveys Highly Active T-Cell Effector Functions

et al. 2005

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The genes for the alpha and beta chains of a highly reactive anti-MART-1 T-cell receptor were isolated from T-lymphocytes that mediated in vivo regression of tumor in a patient with metastatic melanoma. These genes were cloned and inserted into MSCV-based retroviral vectors. After transduction, greater than 50% gene transfer efficiency was demonstrated in primary T-lymphocytes stimulated by an anti-CD3 antibody. The specificity and biologic activity of TCR gene-transduced T-cells was determined by cytokine production after coculture of T-cells with stimulator cells pulsed with MART-1 peptide. The production of interferon-gamma and granulocyte macrophage-colony stimulating factor (GM-CSF) was comparable to highly active MART-1 specific peripheral blood lymphocytes (PBL) in the amount of cytokine produced and transduced cells recognized peptide pulsed cells at dilutions similar to cytotoxic T lymphocyte (CTL) clones. Human leukocyte antigen (HLA) class I restricted recognition was demonstrated by mobilization of degranulation marker CD107a, by cell lysis, by cytokine production, and by proliferation in the presence of HLA-A2-positive but not HLA-A2-negative melanoma cell lines. Similar data was obtained when tumor-infiltrating lymphocytes (TIL) were transduced with the TCR genes, converting previously nonreactive cells to tumor reactive cells. TCR-transduced T-cells are thus attractive candidates for evaluation in cell transfer therapies of patients with cancer.

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Section: Introductionmentioning

confidence: 99%

Transfer of a TCR Gene Derived from a Patient with a Marked Antitumor Response Conveys Highly Active T-Cell Effector Functions

et al. 2005

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“…5,7,8,19,20 Within a short period of time after their introduction, A103/M2-7C10 and T311 have become popular markers for diagnostic use in pathology, especially for the workup of amelanotic metastatic tumors and detection of micrometastases in sentinel lymph node of patients with primary cutaneous melanoma. [1][2][3]6,[10][11][12][13][14]17,28 The mAb D5 may also be helpful in selected settings, but its staining profile is less restricted to melanocytes than T311 and A103/M2-7C10 5,22,24,25,28 because the antibody was generated to a protein derived from the consensus region shared by various isoforms of microphthalmia transcription factor (MITF). Only one isoform (MITF-M) is melanocyte-specific.…”

mentioning

confidence: 99%

Immunohistochemical Analysis of Novel Monoclonal Antibody PNL2 and Comparison With Other Melanocyte Differentiation Markers

Busam

Kucukgol²,

Satô³

et al. 2005

The American Journal of Surgical Pathology

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PNL2 is a novel monoclonal antibody, which has recently been introduced as an immunohistochemical reagent to stain melanocyte and tumors derived thereof. In the present study, we analyzed the immunoreactivity of this mAb in various normal tissues, melanocytic nevi, primary and metastatic melanoma, nonmelanocytic tumors, including histologic mimickers of melanoma as well as angiomyolipoma, and multiple cell lines derived from different tumors types. We used several tissue microarray panels as well as selected conventional sections from tissue blocks. For metastatic melanoma, immunoreactivity for PNL2 was compared with A103 (Melan-A/MART-1), T311 (tyrosinase), HMB45 (gp100), and D5 (MITF). Positive staining with PNL2 was found in normal melanocytes and neutrophils, but no other normal cell type. Among melanocytic lesions, both benign nevi as well as primary malignant melanomas, especially epithelioid variants thereof, were commonly immunopositive. Only 1 of 13 desmoplastic melanomas reacted with PNL2. PNL2 showed high sensitivity for metastatic melanoma (87%). In comparison, 82% of metastatic melanomas were positive for A103, 76% for HMB45, 92% for T311, and 84% for D5. The combined use of all five reagents minimized the number of immunonegative cases. None of the selected nonmelanocytic tumors (carcinomas or soft tissue neoplasms) was positive for PNL2 in this series except for angiomyolipomas and chronic myeloid leukemias and 1 single case of a malignant peripheral nerve sheath tumor with heterologous differentiation (malignant Triton tumor). Despite its reactivity with neutrophils, PNL2 appears to be a valuable supplementary reagent for the diagnosis of melanocytic tumors.

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“…As the role of Melan-A in the immunogenicity of melanoma changes in its expression level, it might have implications for the progression of the disease and prognosis, as well as immunotherapy. In 2001, two groups reported loss of expression of Melan-A with the progression of primary melanomas [4,30]. Berset et al [4] used immunohistochemistry to assess the expression of Melan-A and found a negative correlation between expression level and Breslow thickness.…”

Section: Introductionmentioning

confidence: 98%

“…Immunohistochemistry is standard practice in the diagnosis of problematic melanocytic lesions, especially for distinguishing melanomas from histologically similar neoplasms and/or for detecting small numbers of melanoma cells, such as those present in early infiltration stages. The three most frequently used antibodies are HMB-45, S-100 and Melan-A [3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

“…Kageshita et al [22] reported the expression of MART-1 in all 28 primary, 29 metastatic melanomas and 18 pigmented naevi investigated. Berset et al [4] detected the expression of Melan-A in 90% of primary melanomas. Megahed et al [6], using Melan-A, demonstrated invasive melanomas in 30% of patients classified as melanoma in situ in the earlier routine histopathological examinations.…”

Section: Introductionmentioning

confidence: 99%

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Skin layer-specific Melan-A expression during progression of human cutaneous melanoma: implications for diagnostic applications of the marker

Sztramska

Dymerska²,

Chwirot³

2008

Melanoma Research

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Melan-A is widely used in the diagnostics of human melanoma. The immunogenicity of this glycoprotein makes it a potential target in immunotherapy and several authors have suggested its potential as a prognostic factor. Up to now there has been no clear direct evidence of changes of Melan-A expression during the progression of melanoma. We have performed objective immunohistochemical assessment of the expression of Melan-A in benign naevi and melanomas at different stages of progression. Our results show a complex pattern of changes in the expression of Melan-A in melanomas depending on the location of melanoma cells within individual skin layers. The expression of the antigen during tumour progression significantly decreases for melanoma cells located in the granular/spinous layer (r = -0.94, P = 0.02) and increases for the papillary layer (r = 0.99, P = 0.002) and reticular layer (r = 0.89, P = 0.04). It should also be emphasized that from the Clark II level of progression the melanomas can be detected with high sensitivity and specificity using a simple cut-off test based on the determination of Melan-A expression in tumour cells located within the papillary layer.

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Expression of melan‐a/MART‐1 antigen as a prognostic factor in primary cutaneous melanoma

Cited by 8 publications

References 0 publications

Transfer of a TCR Gene Derived from a Patient with a Marked Antitumor Response Conveys Highly Active T-Cell Effector Functions

Transfer of a TCR Gene Derived from a Patient with a Marked Antitumor Response Conveys Highly Active T-Cell Effector Functions

Immunohistochemical Analysis of Novel Monoclonal Antibody PNL2 and Comparison With Other Melanocyte Differentiation Markers

Skin layer-specific Melan-A expression during progression of human cutaneous melanoma: implications for diagnostic applications of the marker

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