mart-1-antigen and Brain-Neoplasms

Melanoma of the skin is characterised by a high metastatic potential, but reports of metastasis to the tongue are rare. We report a case of skin melanoma with metastasis to the lymph nodes, tongue and brain.. This report highlights the clinical and histological features of oral metastatic melanoma.. A 72-year-old man was seen with a nodule on the tongue. The differential diagnosis included salivary gland tumour, lymphoma and metastatic melanoma. His medical history revealed treatment for melanoma in the periumbilical region and micrometastases in the inguinal lymph nodes. An incisional biopsy was obtained and histological analysis showed the presence of a solid, epithelioid malignant tumour of monotonous appearance infiltrating the skeletal musculature. Immunohistochemistry showed reactivity of neoplastic cells to anti-HMB45, anti-melan A and anti-S100 antibodies and negativity for anti-PAN cytokeratin, confirming the diagnosis of metastatic melanoma.. The present findings highlight the importance of a complete medical evaluation of the patient by anamnesis to identify possible oral repercussions of primary diseases in other organs and/or systems.

Topics: Aged; Brain Neoplasms; Diagnosis, Differential; gp100 Melanoma Antigen; Humans; Immunohistochemistry; Lymphatic Metastasis; Male; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; S100 Proteins; Skin Neoplasms; Tongue Neoplasms

Conjunctival melanoma is a relatively rare malignancy. It is presented as pigmented nodule in any area of conjunctiva, amelanotic tumors are pink with smooth appearance. The authors describe an amelanotic melanoma of the conjunctiva in an 82-year-old female patient. Cytological, histopathological and immunohistochemical studies revealed an invasive amelanotic melanoma exhibiting S-100 and MART-1 positivity. The patient undervent surgical and chemotherapy treatment and three years after the initial treatment is in the terminal stage of metastatic disease. Absence of pigmentation delayed early clinical detection and treatment. Awareness of this nonpigmented melanoma is crucial for early recognition and appropriate management.

Topics: Aged, 80 and over; Biomarkers, Tumor; Biopsy; Brain Neoplasms; Conjunctival Neoplasms; Female; Humans; MART-1 Antigen; Melanoma, Amelanotic; S100 Proteins; Tomography, X-Ray Computed

SOX-9 was originally identified as a master regulator gene that plays a role in the differentiation of mesenchymal cells to chondrocytes. Since then, SOX-9 has been implicated in neural crest development and has emerged as a transcriptional regulator of melanogenesis. Because the role of immunohistochemical detection of SOX-9 in the routine diagnosis of melanoma has not been previously described, we attempted to elucidate the spectrum and labeling characteristics of this antibody in a large cohort of patients with metastatic melanoma. We analyzed the expression of SOX-9 on sections of metastatic melanoma in a tissue microarray and compared the expression of this marker with 3 commonly used melanocytic markers (MART-1, HMB-45 antigen, and S-100 protein). SOX-9 expression was noted in 52 of the 62 cases (83.9%). In comparison, HMB-45 was positive in 53 of the 62 cases (85.5%), MART-1 was positive in 59 of the 62 cases (95.1%), and S-100 protein was positive in 57 of the 62 cases (95%). Interestingly, there were 5 tumors that were negative for 2 or more markers while being positive for SOX-9. Furthermore, 3 of these were negative for all markers except for SOX-9. Our study illustrates that SOX-9 is expressed in a high percentage of melanomas. Furthermore, SOX-9 may be a useful adjunct in the work-up of metastatic melanoma, in such cases where the tumor is negative for the other commonly used melanocytic markers. Last, our data confirm that SOX-9 is not a specific marker for tumors of cartilage lineage and may be expressed in other tumors of neural crest origin.

Topics: Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Brain Neoplasms; Cell Nucleus; Diagnostic Errors; Female; Humans; Immunoenzyme Techniques; Male; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Retrospective Studies; S100 Proteins; Skin Neoplasms; SOX9 Transcription Factor; Tissue Array Analysis; Young Adult

Melanoma is the major cause of skin cancer death worldwide. Parkinson's disease is a neurodegenerative disorder that is caused by mutation of alpha-synuclein or other genes. Importantly, epidemiological studies have reported co-occurrence of melanoma and Parkinson's disease, suggesting that these two diseases could share common genetic components.. Recently, we found that human melanoma cell lines highly express alpha-synuclein, whereas the protein is undetectable in the non-melanoma cancer cell lines tested. To investigate the expression of alpha-synuclein in human melanoma tissues, we immunostained sections of melanoma, nevus, non-melanocytic cutaneous carcinoma, and normal skin. alpha-Synuclein was positively detected in 86% of the primary and 85% of the metastatic melanoma sections, as well as in 89% of nevus sections. However, alpha-synuclein was undetectable in non-melanocytic cutaneous carcinoma and normal skin.. The Parkinson's disease-related protein, alpha-synuclein, is expressed in both malignant and benign melanocytic lesions, such as melanomas and nevi. Although alpha-synuclein cannot be used to distinguish between malignant and benign melanocytic skin lesions, it might be a useful biomarker for the diagnosis of metastatic melanoma.

Topics: Adult; Aged; alpha-Synuclein; Antigens, Neoplasm; Biomarkers, Tumor; Brain Neoplasms; Cell Line, Tumor; Female; Humans; Male; MART-1 Antigen; Melanins; Melanoma; Middle Aged; Neoplasm Proteins; Nevus; Parkinson Disease; Pigmentation; Retinoblastoma; 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

Some immunotherapeutic approaches based on melanoma-associated antigens rely on in vitro cultivation of melanoma cells. A beneficial effect of interferons has been shown in melanoma. This study aimed to determine whether stimulation of patient-derived melanoma short-term cell cultures using interferon-alpha and -gamma changes the expression pattern of melanoma-associated antigens. Lymph node, skin and brain metastases were cultivated for up to 3 weeks and treated with interferon-alpha, interferon-gamma or mock stimulation. Expression of the melanoma-associated antigens MAGE-3, MelanA/MART-1 and tyrosinase was determined by flow cytometry and compared with the expression pattern of HLA class I molecules. We found consistently enhanced expression of HLA class I molecules, whereas the melanoma-associated antigens showed mixed responses, with moderate induction, suppression or no visible effect. The reaction to interferon stimulation was similar for all the antigens examined within a single melanoma cell culture. In contrast to the HLA class I molecules, which showed induced expression with interferon, the melanoma-associated antigens showed a varied response to interferon stimulation. Differential reaction to interferon stimulation is of importance to immunotherapeutic modalities and might influence progression of the disease. We therefore suggest that evaluation of variation in melanoma-associated antigen expression in the clinical setting may help to identify patients who would profit from adjuvant interferon therapy.

Topics: Animals; Antibodies, Monoclonal; Antigens; Antigens, Neoplasm; Brain Neoplasms; Cell Line; Cell Separation; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Genes, MHC Class I; gp100 Melanoma Antigen; Humans; Interferon-alpha; Interferon-gamma; Interferons; Lymphatic Metastasis; MART-1 Antigen; Melanoma; Membrane Glycoproteins; Mice; Monophenol Monooxygenase; Neoplasm Proteins; Reverse Transcriptase Polymerase Chain Reaction; Skin Neoplasms; Tumor Cells, Cultured; Up-Regulation

Melanoma frequently metastasizes to the central nervous system (CNS). The diagnosis of CNS metastases typically is made following the onset of clinical symptoms. Thus, more sensitive diagnostic approaches are needed to identify subclinical CNS metastases. Currently, standard cytologic analysis of the cerebrospinal fluid (CSF) is limited by its poor sensitivity. A more sensitive assay was therefore developed using multiple reverse transcriptase-polymerase chain reaction (RT-PCR) markers. CSF was collected and assessed by RT-PCR for three known melanoma-associated markers (MAGE-3, MART-1, and tyrosinase) to detect occult metastatic melanoma cells in the CSF of 37 American Joint Committee on Cancer (AJCC) stage IV melanoma patients. Cytologic analysis of CSF was performed on all patients, and immunohistochemistry (IHC) analysis was performed on 33 CSF samples using anti-S100 and anti-HMB-45 antibodies. Only one patient (3%) had tumor-positive CSF cytology and IHC upon entry into the study, whereas 12 patients (32%) were positive for at least one RT-PCR marker. The correlation between CSF RT-PCR positivity of MART-1 and/or MAGE-3 and the development of CNS metastases at 3 mo was significant (p = 0.04). Fifteen of 37 patients (41%) had either positive MRI and/or positive RT-PCR results. Multimarker RT-PCR is more informative and sensitive than cytology/IHC in assessing the CSF of melanoma patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Brain Neoplasms; Disease-Free Survival; DNA, Neoplasm; Female; Humans; Male; MART-1 Antigen; Melanoma; Middle Aged; Monophenol Monooxygenase; Neoplasm Proteins; Predictive Value of Tests; Reverse Transcriptase Polymerase Chain Reaction; Skin Neoplasms

Dendritic cells (DCs) are potent antigen-presenting cells that have been shown to play a critical role in the initiation of host immune responses against tumor antigens. In this study, a recombinant adenovirus vector encoding the melanoma-associated antigen, MART-1, was used to transduce murine DCs, which were then tested for their ability to activate cytotoxic T lymphocytes (CTLs) and induce protective immunity against B16 melanoma tumor cells implanted intracranially.. Genetic modification of murine bone marrow-derived DCs to express MART-1 was achieved through the use of an E1-deficient, recombinant adenovirus vector (AdVMART1). Sixty-two C57BL/6 mice were immunized by subcutaneous injection of AdVMART-1-transduced DCs (23 mice), untransduced DCs (17 mice), or sterile saline (22 mice). Using the B16 murine melanoma, which naturally expresses the MART-1 antigen, all the mice were then challenged intracranially with viable, unmodified syngeneic B16 tumor cells 7 days later. Splenocytes obtained from representative animals in each group were harvested for standard cytotoxicity and enzyme-linked immunospot assays. The remaining mice were followed for survival. Immunization of C57BL/6 mice with DCs transduced with AdVMART1-DC elicited the development of antigenspecific CTL responses. As evidenced by a prolonged survival curve when compared with control-immunized mice harboring intracranial B16 tumors, AdMART1-DC vaccination was able to elicit partial protection against central nervous system (CNS) tumor challenge in vivo. However, this CNS antitumor immunity was weaker than that previously demonstrated against subcutaneous B16 tumors in which the same vaccination strategy was used.. These data suggest that immune responses generated against CNS tumors by DC-based vaccines may be different from those obtained against subcutaneous tumors.

Topics: Adenoviridae; Animals; Antigens, Neoplasm; Brain Neoplasms; Cells, Cultured; Cytokines; Dendritic Cells; Disease Models, Animal; Female; Humans; Immunization; MART-1 Antigen; Melanoma; Mice; Mice, Inbred C57BL; Neoplasm Proteins; Neoplasm Transplantation; Spleen; T-Lymphocytes, Cytotoxic; Transduction, Genetic; Xenograft Model Antitumor Assays