mart-1-antigen and Carcinoma

Exosomes derived from tumours are small vesicles released in vitro by tumour cell lines in culture supernatants. To assess the role of these exosomes in vivo, we examined malignant effusions for their presence. We also investigated whether these exosomes could induce production of tumour-specific T cells when pulsed with dendritic cells.. We isolated exosomes by ultracentrifugation on sucrose and D(2)O gradients of 11 malignant effusions. We characterised exosomes with Western blot analyses, immunoelectron microscopy, and in-vitro stimulations of autologous T lymphocytes.. Malignant effusions accumulate high numbers of membrane vesicles that have a mean diameter of 80 nm (SD 30). These vesicles have antigen-presenting molecules (MHC class-I heat-shock proteins), tetraspanins (CD81), and tumour antigens (Her2/Neu, Mart1, TRP, gp100). These criteria, including their morphological characteristics, indicate the similarities between these vesicles and exosomes. Exosomes from patients with melanoma deliver Mart1 tumour antigens to dendritic cells derived from monocytes (MD-DCs) for cross presentation to clones of cytotoxic T lymphocytes specific to Mart1. In seven of nine patients with cancer, lymphocytes specific to the tumour could be efficiently expanded from peripheral blood cells by pulsing autologous MD-DCs with autologous ascitis exosomes. In one patient tested, we successfully expanded a restricted T-cell repertoire, which could not be recovered carcinomatosis nodules.. Exosomes derived from tumours accumulate in ascites from patients with cancer. Ascitis exosomes are a natural and new source of tumour-rejection antigens, opening up new avenues for immunisation against cancers.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinoma; Cytoplasmic Vesicles; Dendritic Cells; Female; Humans; Male; MART-1 Antigen; Middle Aged; Neoplasm Proteins; Pleural Effusion, Malignant; Tumor Cells, Cultured

A 47-year-old woman developed metastatic melanoma to the right ovary 14 years after the enucleation of the right eye for a choroidal spindle cell melanoma. An immunohistochemical study was performed on paraffin sections of both primary and metastatic melanoma specimens to identify markers of both aggressive phenotype and metastatic potential with particular attention to the anomalous expression of cytokeratin intermediate filament proteins. Neoplastic cells of both primary and metastatic tumors immunostained positively for S-100, HMB45, MART-1, and vimentin antibodies, but they were negative for cytokeratins 1-19, 8, 18, and 8,18; <10% of neoplastic cells in both the primary and the metastatic melanomas immunostained for Ki-67 proliferating antigen using MIB-1 antibody. We speculate that the indolent behavior of this ovarian metastasis is reflected by the absence of coexpression of cytokeratins 8 and 18 with vimentin. This case supports the practical value of using this panel of antibodies to evaluate the aggressive potential of uveal melanomas.

Topics: Antigens, Neoplasm; Carcinoma; Choroid Neoplasms; Female; Humans; Immunohistochemistry; Immunophenotyping; Intermediate Filament Proteins; Keratins; Ki-67 Antigen; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Ovarian Neoplasms; S100 Proteins; Time Factors; Vimentin

The purpose of this study was to test different malignant non-melanocytic tumours with the commercially available antibody Melan-A to examine its diagnostic specificity and to compare the S100, Melan-A and HMB-45 reactivity in various melanocytic lesions.. Seventy-three benign and malignant melanocytic lesions and 31 cases of non-melanocytic tumours, sarcomas, carcinomas and carcinoids, were selected. Immunohistochemical staining of paraffin sections, following a high temperature antigen unmasking technique, was performed. Melan-A stains junctional and dermal melanocytes in all benign melanocytic lesions with the exception of neuro-naevoid areas. The epithelioid and the spindle cells in malignant melanomas did not show considerable difference in their Melan-A reactivity. The predominantly spindle cell type mucosal melanomas contained more Melan-A-positive cells than HMB-45-positive cells and similar results were observed in metastatic malignant melanomas. In desmoplastic melanomas the positivity of Melan-A was not consistent. None of the sarcomas, carcinomas and carcinoids expressed Melan-A. Almost all soft tissue tumours, except for two malignant gastrointestinal stromal tumours, were unreactive for HMB-45. These two cases did not react with Melan-A antibody.. Melan-A is a useful additional marker to differentiate non-melanocytic tumours from primary or metastatic melanoma. In melanocytic lesions the Melan-A staining pattern is similar to S100, but seems to be more specific. In desmoplastic melanomas, however, the variable Melan-A staining further necessitated detailed histological examination and the use of the S100 reaction.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoid Tumor; Carcinoma; Humans; Immunohistochemistry; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Neoplasm Proteins; S100 Proteins; Sarcoma; Skin Neoplasms; Soft Tissue Neoplasms