Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have shown previously that peripheral blood lymphocytes (PBL) of patients with metastatic melanoma include cytotoxic T-cell clones that recognize Melan-A/MART-1 in a HLA-A2-restricted fashion. Such clones preferentially use the variable (V) regions TCRBV14 or TCRBV7 in the beta-chain of their T-cell receptor (TCRB). It was not known, however, whether this finding is associated with the presence of the HLA-A2 allele in tumor tissue and whether evidence of the predominance of these TCRBV families can also be observed in primary tumor tissue. To address these issues, we have used a semiquantitative PCR to examine the TCRBV repertoire in six HLA-A2-matched primary melanomas in comparison with their autologous PBL. Although each patient had his or her own pattern of skewed TCRBV utilization, in all patients, T-cells that used TCRBV14 were significantly overrepresented in the neoplastic site compared with PBL. All of the primary tumors studied had detectable expression of Melan-A/MART-1 and gp100, and immunohistochemical analysis confirmed the presence of the HLA-A2 allele. Additional samples of Melan-A/MART-1-positive, gp100-positive primary melanomas from six non-HLA-A2 patients and four autologous normal skin controls failed to reveal a TCRBV14 predominance in such tissues. These results point to a role of TCRBV14 T lymphocytes in the HLA-A2-restricted immune recognition of primary melanomas.
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PMID:Overexpression of the T-cell receptor beta-chain variable region TCRBV14 in HLA-A2-matched primary human melanomas. 761 74

We developed the techniques of lymphatic mapping and sentinel node (SN) biopsy to improve the management of patients with high-risk (thick and deep) primary melanoma. The SN is the first lymph node on the direct lymphatic drainage path from the primary tumor. This node is uniquely immune-modulated by the primary tumor and is the node most likely to contain the earliest stages of metastases. Accurate assessment of the SN requires careful evaluation of multiple sections removed from the areas of the node most likely to contain tumor. These sections are stained with hematoxylin and eosin and by immunohistochemistry with antibodies directed to tumor-associated markers (S-100, HMB-45, and Melan-A/MART-1) in the case of melanoma and to cytokeratins for breast cancer. Studies are in progress to determine whether molecular biology techniques will detect additional nodes that contain truly occult tumor deposits.
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PMID:Current practice and future directions in pathology and laboratory evaluation of the sentinel node. 1159 89

Melanoma is a devastating disease frequently encountered within both veterinary and human medicine. Molecular changes linked with neoplastic transformation of melanocytes include mutations in genes that encode proteins intrinsic to the regulatory pathways of two tumor suppressor proteins (retinoblastoma protein and p53), proto-oncogene mutation to oncogenes, altered expression of epithelial cadherin and CD44 adhesion molecules, and upregulation of angiogenic factors and other growth factors. Histologic evaluation of the primary mass is the most common means of diagnosis, with cytology used more frequently to document metastasis. Melanoma's highly variable histologic and cytologic patterns can make diagnosis by either method problematic. Adherent epithelioid morphology, including signet ring forms, and nonadherent round and spindle forms are recognized, with pigmentation an inconsistent finding. The site of the tumor, the thickness of the primary tumor or depth of invasion, and the number of mitotic figures per high-power field or per millimeter are used histologically to predict biologic behavior, whereas site and degree of pleomorphism are typically used for cytologic preparations. Diagnosis of amelanotic melanoma can be aided by ancillary diagnostic techniques. Tumor cells are usually positive for vimentin, S100, neuron-specific enolase, and Melan-A, and negative for cytokeratin. Melan-A as a positive marker is not as sensitive as the others are but is likely more specific. Monoclonal antibodies to human melanosome-specific antigens 1 and 5 cross-react with canine antigens for a combined sensitivity rate of 83%. Mouse monoclonal antibody IBF9 specifically recognizes canine melanoma antigen and also has good sensitivity. Serologic markers, including cytokines, cell adhesion molecules, and melanoma-inhibitory activity, are being investigated as potential sentinels of melanoma. Currently, there is no single diagnostic technique capable of differentiating benign from malignant melanocytic neoplasms or predicting survival time.
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PMID:A comparative review of melanocytic neoplasms. 1245 Jan 97

Malignant melanoma is known to display tremendous histologic diversity. One rare variant is the rhabdoid phenotype, so called because of the appearance of cells resembling rhabdomyoblasts seen in malignant rhabdoid tumors of the kidney. We present the histologic, immunohistochemical, and ultrastructural features of a malignant melanoma composed entirely of rhabdoid cells. A 62-year-old man presented with a 6.5-cm lung mass. Although presumed to be a metastatic lesion, extensive workup failed to reveal a primary tumor site. Histologic sections showed a mass composed entirely of polygonal neoplastic cells with prominent nucleoli and large hyaline cytoplasmic inclusions. The tumor cells were strongly immunoreactive with S100 protein, vimentin, and CD56, and were focally reactive with Mart-1. Tumor cells were negative for Melan-A, tyrosinase, HMB-45, AE1/AE3, cytokeratin (CK) 7, CK8/ 18, CK20, CK903, CAM 5.2, epithelial membrane antigen, smooth muscle actin, desmin, leukocyte common antigen, Bcl-2, CD3, CD20, CD30, CD138, kappa and lambda light chains, CD68, CD34, factor VIII, synaptophysin, and glial fibrillary acidic protein. Electron microscopy showed cytoplasmic whorls of intermediate filaments containing entrapped rough endoplasmic reticulum, mitochondria, and lipid. Recognition of this rare variant of malignant melanoma is important in the evaluation of tumors with rhabdoid morphology.
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PMID:Malignant melanoma with a rhabdoid phenotype: histologic, immunohistochemical, and ultrastructural study of a case and review of the literature. 1516 28

Tumor-reactive T cells play an important role in cancer immunosurveillance. Applying the multimer technology, we report here an unexpected high frequency of Melan-A-specific CTLs in a melanoma patient with progressive lymph node metastases, consisting of 18 and 12.8% of total peripheral blood and tumor-infiltrating CD8+ T cells, respectively. Melan-A-specific CTLs revealed a high cytolytic activity against allogeneic Melan-A-expressing target cells but failed to kill the autologous tumor cells. Loading of the tumor cells with Melan-A peptide reversed the resistance to killing, suggesting impaired function of the MHC class I antigen processing and presentation pathway. Mutations of the coding region of the HLA-A2 binding Melan-A26-35 peptide or down-regulation of the MHC class I heavy chain, the antigenic peptide TAP, and tapasin could be excluded. However, PCR and immunohistochemical analysis revealed a deficiency of the immunoproteasomes low molecular weight protein 2 and low molecular weight protein 7 in the primary tumor cells, which affects the quantity and quality of generated T-cell epitopes and might explain the resistance to killing. This is supported by our data, demonstrating that the resistance to killing can be partially reversed by pre-exposure of the tumor cells to IFN-gamma, which is known to induce the immunoproteasomes. Overall, this is the first report of an extremely high frequency of tumor-specific CTLs that exhibit competent T-cell-effector functions but fail to lyse the autologous tumor cells. Immunotherapeutic approaches should not only focus on the induction of a robust antitumor immune response, but should also have to target tumor immune escape mechanisms.
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PMID:High frequency of functionally active Melan-a-specific T cells in a patient with progressive immunoproteasome-deficient melanoma. 1534 21

Melanoma can show a broad spectrum of immunoreactivity and exhibit aberrant expression of antigens or changes in immunophenotype, particularly at metastatic sites. We studied 70 primary melanomas and their metastases with a broad panel of immunohistochemical markers using a tissue microarray technique to determine possible antigenic shift between the primary lesions and their metastases. Representative tissue cores were taken and processed from each case, and the tissue microarrays were stained by standard methods using antibodies to vimentin, bcl-2, CD117, carcinoembryonic antigen, epithelial membrane antigen, S-100 protein, HMB-45, cytokeratin AE1/AE3, Melan-A, TTF-1, CD99, and tyrosinase. Histologically, all the melanomas were of the classic epithelioid type. A slight increase in the expression of Melan-A was noted in metastatic lesions as opposed to the primary tumors (63% vs. 48.4%). Expression of other melanoma-associated markers, including S-100 protein and tyrosinase was only slightly decreased at metastatic sites as opposed to the primary tumor. Increased aberrant expression of epithelial-associated markers, including epithelial membrane antigen and cytokeratin AE1/AE3 was also noted in the metastases. bcl-2, CD117, and TTF-1 also showed a modest increase in antigenic expression at metastatic sites over the primary lesions. The results of this study demonstrated minimal antigenic shift between primary and metastatic melanoma for some of the more conventional melanocytic markers, it showed increased expression of aberrant markers and oncogene expression at metastatic sites.
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PMID:Expression of immunohistochemical markers in primary and metastatic malignant melanoma: a comparative study in 70 patients using a tissue microarray technique. 1809 85

Gastrointestinal malignant melanomas, either primary or metastatic, are rare and overlooked tumors. There is also controversy regarding the actual existence of primary melanoma in the gastrointestinal tract apart from the esophagus and anorectal regions, where melanocytes normally exist. A case of malignant melanoma in the cecum is presented. The patient was a 30- year-old male who presented to the hospital for abdominal pain and diarrhea. The tumor was located mainly in the submucosa and measured 14x11x4.5 cm. The cut surface was solid, gray-white and fleshy. Histologically, tumor cells were arranged in compact nests or wide cords surrounded by fibrous stroma. The tumor cells had pleomorphic nuclei and quite rich cytoplasm; multinucleated, giant tumor cells were intermingled. Although no tumor cells contained apparent brown pigment, most were found to be positive for S-100 protein, HMB-45, Melan-A, and vimentin. The possibility of a metastatic lesion was considered. While the patient had a history of a pathologically examined dorsal nevus excision two years before, there was no evidence of either cutaneous or ocular primary melanoma at the time of diagnosis. Moreover, a thorough postoperative investigation did not reveal any other lesion in any other site favoring a metastatic spread. There was also no evidence of recurrent disease or metastasis one year after the surgery. This case is presented in view of its rare occurrence in the cecum. The difficulties in the diagnostic course are discussed, together with a literature review on distinguishing a primary mucosal melanoma from a metastatic one from an unknown or regressed cutaneous primary tumor.
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PMID:Colonic malignant melanoma, primary or metastatic? Case report. 2053 13

Adrenocortical carcinosarcoma is an extremely rare and aggressive variant of adrenocortical carcinoma characterized by the presence of both carcinomatous and sarcomatous components, with the latter often showing heterologous differentiation. Due to the rarity and unusual histology, it may pose a diagnostic challenge. In order to increase awareness and identify potential diagnostic pitfalls, we report the ninth case of non-functioning adrenocortical carcinosarcoma in a 45-year-old man who presented with worsening epigastric pain and a left large retroperitoneal mass in close proximity to the body/tail of pancreas and third portion of the duodenum with displacement of the kidney without parenchymal invasion and multiple liver nodules detected by computed tomographic scan. On en bloc resection, the tumor grossly did not involve the pancreas, kidney or colon. Histologically, the tumor was composed of two distinct components - an epithelioid component with granular cytoplasm that stained for synaptophysin, Melan-A, calretinin, and vimentin compatible with adrenocortical differentiation, and a pleomorphic to spindled component that was positive for desmin and myogenin, compatible with rhabdomyosarcomatous differentiation. A wedge biopsy of a liver nodule showed morphologic features similar to the epithelial component of the primary tumor. The patient died three months after surgery due to locoregional and distant recurrence. Adrenocortical carcinosarcoma is a rare malignancy that adds to the differential diagnostic considerations for a retroperitoneal epithelioid malignancy. Awareness of this as a possibility will help in distinguishing this tumor from other carcinomas, melanomas, and true sarcomas.
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PMID:Adrenocortical carcinosarcoma: a case report and review of the literature. 2068 34

A 50-year-old man presented with nausea and abdominal bloating sensation of a few months' duration and was found to have a large adrenal mass that was resected after computed tomography scan evaluation. The histopathologic examination showed epithelioid and spindle cells having clear to granular eosinophilic cytoplasm, and small, central, round to oval nuclei with small nucleoli. The tumor cells demonstrated reactivity for smooth muscle actin, HMB-45, Melan-A, and vimentin, with focal positivity for desmin and S100 protein and negative staining for inhibin, synaptophysin, and chromogranin. A diagnosis of perivascular epithelioid cell tumor was made. Perivascular epithelioid cell tumors can arise in a variety of locations, including omentum/mesentery, female genital tract, pelvic soft tissues, skin, and falciform ligament, but an adrenal primary tumor has not been previously reported, to the best of our knowledge. The differential diagnosis is broad and site-dependant and in our case includes several neoplasms with clear cells that can involve the adrenal gland, including a primary adrenocortical neoplasm. A review of the related literature and discussion of the differential diagnoses are presented.
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PMID:Adrenal perivascular epithelioid cell tumor: a case report with discussion of differential diagnoses. 2146 69

Programmed death 1 (PD-1) is known as an important factor for the development of tolerogenicity. This has been proven in chronic viral infections and different tumor models. To address the role of PD-1 and its ligand programmed death ligand 1 (PD-L1) in different stages of malignant melanoma, we investigated peripheral blood and tumor tissues in regard to overall survival (OS) and prognostic relevance. One hundred samples of peripheral blood mononuclear cells from HLA-A2(+) patients with malignant melanoma (Stages I-IV) were analyzed in seven color FACS combined with multimer analyses for the immunodominant epitope of Melan-A (peptide A2/Melan-A(p26-35mod) ). Corresponding formalin-fixed paraffin-embedded tissues of primary tumor and distant organ metastases from 37 cases were analyzed by immunohistochemistry for Melan-A, PD-L1 and PD-1 expression. Compared to the total CD8(+) T cell population, PD-1 expression by A2/Melan-A(+) CD8(+) T cells was over-represented in melanoma stages III and IV (p < 0.001). Although elevation of PD-1(+) Melan-A(+) CD8(+) T cells had no significant influence on OS, a positive correlation was observed between PD-L1 expression on melanoma cells and OS (p = 0.05). Correlation of advanced tumor stage with increased A2/Melan-A-multimer(+) PD-1(+) T cells in the peripheral blood suggest that blocking of PD-1 could have therapeutic potential in advanced stage melanoma.
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PMID:PD-1 expression on Melan-A-reactive T cells increases during progression to metastatic disease. 2171 61


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