mart-1-antigen and Breast-Neoplasms

The sentinel lymph nodes are the most likely site of nodal metastasis. Their focused analysis results in upstaging cancers, although the extra yield from a more intensive work-up is generally dominated by micrometastases and isolated tumor cells. Nodal staging is generally done to reflect systemic spread of solid tumors and guide treatment accordingly. However, in general, the two processes of haematogenous and lymphogenic spread are not causally interrelated, and the extrapolation from low-volume nodal involvement to systemic involvement and therapeutic consequences of this extrapolation are still under investigation.

Topics: Antigens, Neoplasm; Breast Neoplasms; Colorectal Neoplasms; Female; Humans; Immunohistochemistry; Lymph Nodes; Lymphatic Metastasis; MART-1 Antigen; Melanocytes; Melanoma; Neoplasm Proteins; Neoplasm Staging; Reverse Transcriptase Polymerase Chain Reaction; Sentinel Lymph Node Biopsy

A group of lesions show morphologic and immunophenotypic evidence of differentiation toward a putative perivascular epithelioid cell. These so-called PEComas include angiomyolipoma, lymphangiomyoma, lymphangioleiomyomatosis, renal capsuloma, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres, and clear cell "sugar" tumor. PEComas are characterized by strong immunoreactivity with the HMB45 antibody and variable expression of muscle markers. This family of lesions may be composed of a spectrum of cells from epithelioid to spindle cells with clear to granular eosinophilic cytoplasm. One member of this family, composed of epithelioid cells with glycogen-rich clear cytoplasm, is descriptively called a clear cell "sugar" tumor. This tumor, originally described in the lung, is being recognized increasingly in extrapulmonary sites. We report a case of a primary extrapulmonary clear cell "sugar" tumor occurring in the right breast of a 16-year-old girl. The tumor was composed of clear epithelioid cells with abundant glycogen and distinct cell borders. The tumor showed strong immunoreactivity with HMB45 antibody and Melan-A. There was focal vimentin staining. In addition, there was diffuse and strong nuclear staining for progesterone receptor. Antibodies to actins, S-100 protein, cytokeratins (AE1/AE3 and CAM5.2), desmin, and estrogen receptor were negative. The tumor was completely excised, and the patient is well without evidence of disease 9 months postexcision.

Topics: Adenocarcinoma, Clear Cell; Adolescent; Antigens, Neoplasm; Biomarkers, Tumor; Breast Neoplasms; Cytoplasm; Female; Glycogen; Humans; Immunohistochemistry; MART-1 Antigen; Melanoma-Specific Antigens; Neoplasm Proteins

Melanoma is the second most common non-hematopoietic malignancy after carcinomas to metastasize to the breast and often appears as a well-circumscribed, dense nodule on imaging. Although metastatic lesions presenting as bilateral cysts have been reported, this presentation is not common and may mimic benign breast cysts. We present a challenging case of metastatic melanoma presenting as bilateral breast cysts with spindled cytomorphology in a patient with a history of mammary carcinoma. Discordance between the spindled cytomorphology and the morphology of the core biopsy, which was similar to the patient's primary breast cancer, allowed for entertainment of other tumors and disease processes. Confirmatory immunostaining of the cytology material with HMB-45 was important to establish the diagnosis of metastatic melanoma. Diagn. Cytopathol. 2017;45:446-451. © 2017 Wiley Periodicals, Inc.

Topics: Biomarkers, Tumor; Biopsy, Large-Core Needle; Breast Cyst; Breast Neoplasms; Diagnosis, Differential; Female; gp100 Melanoma Antigen; Humans; Immunohistochemistry; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Middle Aged; S100 Proteins; Skin Neoplasms

The mammary gland can be a site of metastasis in patients with malignant melanoma, which is easily recognized microscopically if clinical information is available. Nonetheless, metastatic melanoma presenting as an isolated mammary tumor can be more challenging to diagnose because it can simulate a primary breast carcinoma clinically and morphologically.. To review metastatic melanoma to the breast, presenting as primary breast carcinomas clinically and morphologically.. The authors report 20 cases of metastatic melanoma clinically presenting as breast tumors. Cases with widespread metastatic presentation were excluded.. Epithelioid and spindle cell tumors predominated, suggesting mammary ductal, papillary, or sarcomatoid carcinoma. Most cases (16 of 20) were submitted for consultation or second opinion owing to their unusual presentation in the breast, or to perform predictive/prognostic immunohistochemical assays. Seven cases had a remarkable phenotypic spectrum expanding the differential diagnosis to large cell lymphoma, leiomyosarcoma, medullary carcinoma, malignant schwannoma, and liposarcoma. Tumor cells were negative for cytokeratin stains and positive for S100 protein, HMB-45, and Melan-A. Negative staining was also observed for epithelial membrane antigen, CD45, desmin, estrogen and progesterone receptors, and human epidermal growth factor receptor 2.. Metastatic melanoma may simulate a broad spectrum of primary breast malignancies. Although the application of a simple panel of antibodies assists in rendering the correct interpretation, lesions presenting as isolated breast tumors may introduce a significant diagnostic difficulty, especially when there is inadequate patient history and/or limited biopsy material. Further challenges are introduced by the extraordinary phenotypic plasticity of metastatic melanoma. Awareness of this pattern variance is essential to avoid inappropriate treatment, especially in cases simulating a "triple negative," poorly differentiated carcinoma of the breast.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Breast Neoplasms, Male; Diagnosis, Differential; Female; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Male; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Middle Aged; S100 Proteins; Skin Neoplasms

Topics: Antigens, Neoplasm; Biopsy; Breast Neoplasms; Dermoscopy; Diagnosis, Differential; Female; Humans; Immunohistochemistry; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Nipples; Paget's Disease, Mammary; S100 Proteins; Skin Neoplasms

Topics: Adrenal Gland Neoplasms; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Breast Neoplasms; Cisplatin; Dacarbazine; Fatal Outcome; Female; Humans; Interferon-beta; Iofetamine; Liver Neoplasms; Lung Neoplasms; MART-1 Antigen; Mastectomy, Modified Radical; Melanoma; Middle Aged; Neoplasm Staging; Nimustine; Nipples; Radiopharmaceuticals; S100 Proteins; Skin Neoplasms; Tamoxifen; Tomography, Emission-Computed, Single-Photon; Vincristine

Topics: Adipose Tissue; Age Factors; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Ductal, Breast; Diagnosis, Differential; Female; Humans; Lymphatic Metastasis; MART-1 Antigen; Melanoma; Neoplasm Invasiveness; Neoplasm Proteins; Neoplasms, Multiple Primary

In previous analyses, dual expression of melanocytic and epithelial molecular markers have been described as indicators of lineage infidelity for breast cancer cells that lose their epithelial identity. Here we demonstrated that this is a much more frequent phenomenon in human breast carcinomas, usually affecting only a part of the tumor. Accordingly we detected, in 18 out of 100 breast carcinomas, immunohistochemically focally positive cells for the melanocytic marker Melan A. The presence and extent of Melan A expression was statistically significantly associated with a reduction in tumor cell differentiation, but not tumor type, size, lymph node metastasis, hormone receptor status or Her-2-neu expression. Microarrays of a further 159 breast cancers showed, in several samples, variably low expression levels of Melan A (and other melanocytic markers) that are consistent with focal expression in many tumors. One case strongly overexpressed Melan A. The transition from an epithelial to a melanocytic phenotype (lineage infidelity) appears to occur much more frequently than previously assumed and occurs in restricted areas of breast cancer during tumor progression, a possible association with a reduction in tumor cell differentiation.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Cell Differentiation; Cell Lineage; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; MART-1 Antigen; Melanocytes; Neoplasm Proteins; Oligonucleotide Array Sequence Analysis

MART1 and MelanA are considered sensitive markers of melanocytic differentiation and are used to increase the detection of melanoma micrometastases in sentinel lymph nodes (SLNs). However, the false-positive rates of these two antibodies have not been adequately evaluated. We examined 217 lymph nodes (LNs) from patients with no history of melanoma: 117 SLNs from breast cancer patients, 79 LNs from other nonmelanoma malignancy patients, and 21 reactive LNs. Capsular melanocytic nevi were identified in 5 SLNs from 5 breast cancer patients by both antibodies. Two of these 5 SLNs with capsular nevus also contain MART1- and MelanA-positive cells within the lymph node parenchyma. Individual immunoperoxidase-positive cells were also identified within the parenchyma of lymph nodes without capsular nevus (9 LNs with MART1 and 3 LNs with MelanA). The false-positive rate is 5.1% for MART1 and 2.4% for MelanA. In conclusion, MART1- or MelanA-positive cells may be present in lymph nodes from patients without melanoma. Therefore, MART1- and MelanA-positive cells in SLNs from melanoma patients, without corresponding atypia or hematoxylin and eosin findings, should be interpreted with caution.

Topics: Antigens, Neoplasm; Biomarkers; Breast Neoplasms; False Positive Reactions; Female; Humans; Immunoenzyme Techniques; Lymph Nodes; MART-1 Antigen; Neoplasm Proteins

The origin of cell lines is critical in defining cell type-specific biological functions. Several reports suggested that the MDA-MB-435 cell line, a cell line extensively used for studying breast cancer biology, has a gene expression pattern most compatible with melanocyte origin. However, we demonstrate that MDA-MB-435 cells express breast-specific or epithelial-specific markers. Also, MDA-MB-435 cells were induced to express breast differentiation-specific proteins and secrete milk lipids as observed in other well-established breast cancer cell lines. Notably, MDA-MB-435 cells also expressed melanocyte-specific proteins as did another highly aggressive breast cancer cell line. MDA-MB-435 xenograft tissue sections stained entirely positive for epithelium-specific markers but only partially positive for melanocyte-specific markers. Thus, MDA-MB-435 is most likely a breast epithelial cell line that has undergone lineage infidelity.

Topics: Animals; Antigens, Neoplasm; Breast Neoplasms; Caseins; Cell Differentiation; Cell Line, Tumor; Cell Lineage; Disease Progression; Female; Humans; Lipids; MART-1 Antigen; Melanocytes; Mice; Mice, Inbred BALB C; Mice, Nude; Mice, SCID; Monophenol Monooxygenase; Neoplasm Proteins; Organ Specificity; Transplantation, Heterologous

Immunization with tumor-associated antigen pulsed dendritic cells (DC) has been shown to elicit both protective and therapeutic antitumor immunity in a variety of animal models and is currently being investigated for the treatment of cancer patients in clinical trials. In this study we show that DC can be generated from peripheral blood mononuclear cells of healthy donors as well as breast and melanoma cancer patients using granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-13 (IL-13) and that these DC have many of the same characteristics as DC differentiated using GM-CSF and IL-4. The DC generated in GM-CSF and IL-13 are CD14- and express high levels of the cell surface markers CD86, HLA-DR, and CD58, as do DC generated in GM-CSF and IL-4. The purity and yield of both DC populations are not significantly different. Furthermore, both populations of DC are effective at presentation of alloantigen as determined in a mixed lymphocyte response, and both are able to process and present soluble tetanus toxoid antigen to CD4+ T cells. Because we are interested in the generation of DC for antigen-specific cytotoxic T lymphocyte (CTL) generation, we compared the ability of peptide-pulsed DC differentiated in GM-CSF and IL-4 versus GM-CSF and IL-13 for the generation of influenza and MART-1 specific CTL. Both populations of DC induced CD3+ CD8+ CD4- and CD56- CTL, which could lyse the appropriate targets in an antigen-specific manner. Finally, both GM-CSF and IL-4 DC and GM-CSF and IL-13 DC yielded similar beta galactosidase expression levels after transduction with recombinant adenovirus containing the LacZ gene. These results suggest that DC generated in GM-CSF and IL-13 may be useful for immunotherapy and gene therapy protocols.

Topics: Antigens, Neoplasm; Breast Neoplasms; Cell Differentiation; Dendritic Cells; Genetic Therapy; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunophenotyping; Immunotherapy; Interleukin-13; Interleukin-4; Leukocytes, Mononuclear; Lymphocyte Culture Test, Mixed; MART-1 Antigen; Melanoma; Neoplasm Proteins; Neoplasms; T-Lymphocytes, Cytotoxic

Evidence is growing for both humoral and cellular immune recognition of human tumor antigens. Antibodies with specificity for antigens initially recognized by cytotoxic T lymphocytes (CTLs), e.g., MAGE and tyrosinase, have been detected in melanoma patient sera, and CTLs with specificity for NY-ESO-1, a cancer-testis (CT) antigen initially identified by autologous antibody, have recently been identified. To establish a screening system for the humoral response to autoimmunogenic tumor antigens, an enzyme-linked immunosorbent assay (ELISA) was developed using recombinant NY-ESO-1, MAGE-1, MAGE-3, SSX2, Melan-A, and tyrosinase proteins. A survey of sera from 234 cancer patients showed antibodies to NY-ESO-1 in 19 patients, to MAGE-1 in 3, to MAGE-3 in 2, and to SSX2 in 1 patient. No reactivity to these antigens was found in sera from 70 normal individuals. The frequency of NY-ESO-1 antibody was 9.4% in melanoma patients and 12.5% in ovarian cancer patients. Comparison of tumor NY-ESO-1 phenotype and NY-ESO-1 antibody response in 62 stage IV melanoma patients showed that all patients with NY-ESO-1(+) antibody had NY-ESO-1(+) tumors, and no patients with NY-ESO-1(-) tumors had NY-ESO-1 antibody. As the proportion of melanomas expressing NY-ESO-1 is 20-40% and only patients with NY-ESO-1(+) tumors have antibody, this would suggest that a high percentage of patients with NY-ESO-1(+) tumors develop an antibody response to NY-ESO-1.

Topics: Antibodies, Neoplasm; Antigens, Neoplasm; Autoantibodies; Breast Neoplasms; Colonic Neoplasms; Enzyme-Linked Immunosorbent Assay; Female; Humans; Lung Neoplasms; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Membrane Proteins; Monophenol Monooxygenase; Neoplasm Proteins; Neoplasms; Ovarian Neoplasms; Proteins; Recombinant Proteins; Repressor Proteins