Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the clinicopathologic features of three cases of malignant melanoma metastatic to the vagina; only one similar case has been previously reported. The age of the patients ranged from 33 to 70 years; two presented with vaginal bleeding. Two patients had a history of a previous primary malignant melanoma, one a preauricular melanoma treated 7 years earlier and the other a vulvar melanoma treated 2 years earlier. In the third case, a primary malignant melanoma was found on the sole of the right foot after the patient had presented with the vaginal metastases. On gross examination, the vaginal tumors were polypoid; two were on the posterior wall and one was on the anterior wall. All were of epithelioid cell type and were positive with S-100 and microphthalmia-transcription factor. Tyrosinase was positive in two cases, HMB-45 was positive in one case, and MART-1 was focally positive in one case. One patient underwent wide local excision of tumor followed by chemotherapy, one patient had intracavitary radiotherapy, and one had palliative radiotherapy to the brain only. The patients died after a follow-up of 3, 14, and 48 months.
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PMID:Metastatic melanoma to the vagina: clinicopathologic and immunohistochemical study of three cases and literature review. 1264 67

Malignant melanoma is one of the most rapidly increasing cancer types, and patients with metastatic disease have a very poor prognosis. Detection of metastatic melanoma cells in circulation may aid the clinician in assessing tumor progression, metastatic potential, and response to therapy. Tyrosinase is a key enzyme in melanin biosynthesis. The gene is actively expressed in melanocytes and melanoma cells. Melan A is a differentiation antigen that is expressed in melanocytes. The presence of these molecules in blood is considered a marker for circulating melanoma cells. In this study, we analyzed the usefulness of this marker combination in evaluating the response to therapy in the blood of 30 patients with malignant melanoma. Circulating cells were detected by a reverse-transcriptase-polymerase-chain reaction. The tyrosinase expression was observed in 9 (30%) patients and Melan A in 19 (63.3%) patients before therapy. Following treatment, the tyrosinase mRNA was detected in only one patient, while Melan A transcripts were still present in 14 patients. We suggest that this molecular assay can identify circulating melanoma cells that express melanoma-associated antigens and may provide an early indication of therapy effectiveness.
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PMID:Detection of circulating melanoma cells by a two-marker polymerase chain reaction assay in relation to therapy. 1268 15

Melanoma lesions that develop in the same patient at different times or simultaneously at different locations may differ antigenically, because malignant melanoma is heterogeneous in terms of its biological, immunological and metastatic properties. The objective of this study was to characterize the molecular profiles of melanoma cells in peripheral blood, lymph nodes and metastatic tissues, employing the messenger RNA (mRNA) expression of tyrosinase, melanoma-inhibiting activity (MIA) and melanoma antigen recognized by T cells-1 (MART-1) as markers. Samples of cells propagated from metastatic sites were obtained from 17 stage III/IV melanoma patients and assayed by reverse transcriptase-polymerase chain reaction (RT-PCR), using specific primers for each marker. In eight patients, marker profiles were analysed in simultaneously obtained specimens of peripheral blood, lymph nodes and metastatic tissues originating from the same patient. Tyrosinase, MIA and MART-1 were expressed in 59%, 76% and 76% of the metastases, respectively. Simultaneously obtained specimens of peripheral blood, lymph nodes and metastatic tissues showed a high degree of homogeneity: 60%, 75% and 20% for tyrosinase, MIA and MART-1, respectively. Our findings suggest that the rather homogeneous expression pattern found in different tumour sites analysed in the same patient is of potential prognostic and therapeutic importance. Furthermore, melanoma lesions may be negative for the expression of antigens such as MART-1, and discrepancies in expression patterns between peripheral blood and metastatic tissues may occur, especially for this marker. Finally, our findings support the notion that molecular screening using an RT-PCR approach is appropriate in this kind of investigation.
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PMID:Molecular detection of MART-1, tyrosinase and MIA in peripheral blood, lymph nodes and metastatic sites of stage III/IV melanoma patients. 1545 91

Reverse transcription polymerase chain reaction (RT-PCR) of tyrosinase mRNA has been applied for the detection of melanoma cells in the peripheral blood, lymph nodes and bone marrow of melanoma patients. We evaluated the diagnostic accuracy of RT-PCR in comparison to standard cytology and immunocytochemistry (ICC) for the identification of melanoma cells in biological fluids other than blood. Tyrosinase expression was evaluated together with standard cytology and ICC (anti-S100, HMB-45 and Melan-A antibodies) in biological fluid samples collected from 17 melanoma patients according to the site of metastatic involvement or clinical suspicion (eight cerebrospinal fluid (CSF) samples; three pleural effusions; four ascites; one bile sample, one pericardial effusion); 17 samples collected from patients with non-melanoma metastatic cancer were used as controls. Tyrosinase expression in the biological fluid sample was compared with the expression determined at the same time in peripheral blood. Positive tyrosinase expression was found in 12/17 melanoma and 3/17 non-melanoma cancer patients. Cytology/ICC showed the presence of neoplastic cells in only 7/12 melanoma samples with positive tyrosinase expression: radiological evidence of disease involvement was found in all these patients (three meningeal, two pleural, two peritoneal). Clear-cut radiological evidence of disease involvement at the sampling site was found in the five patients with negative cytology/ICC and positive RT-PCR (one CSF; four serous membrane effusions); all patients died of disease progression within four months of sampling. The five patients who were negative for both cytology/ICC and RT-PCR did not show any clinical evidence of disease recurrence at the sampling site. Only five of the 12 metastatic patients with positive tyrosinase expression in biological fluid showed positivity for tyrosinase in the peripheral blood. These preliminary results suggest that the analysis of biological fluids other than blood could be considered as a new potential clinical field of application for the tyrosinase mRNA assay.
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PMID:Tyrosinase mRNA RT-PCR analysis as an additional diagnostic tool for the identification of melanoma cells in biological fluid samples other than blood: a preliminary report. 1583 68

The new monoclonal antibody SM5-1 has been shown to have significant advantages in immunohistochemistry of melanoma over currently used antibodies such as HMB-45 or anti-S100. In this study we compared the immunohistological staining pattern of SM5-1 with that of the more recently described antibodies A103 (anti-MART-1) and T311 (anti-Tyrosinase) in 344 paraffin-embedded melanoma specimens, consisting of 101 primary melanomas (77 SSM, 16 NM, 6 ALM, 2 LMM) and 243 melanoma metastases. The overall reactivity of SM5-1 for all the specimens was 92% (318/344) compared with 83% (285/344) for MART-1 and 71% (245/344) for Tyrosinase. Staining of melanoma metastases with SM5-1 was found in 91% (222/243), but only in 77% (187/243) with A103 and 63% (154/243) with T311, respectively. Staining with SM5-1 was more homogenous with 196 of 243 (80%) of metastatic lesions showing 50% or more positively stained cells within the lesions, whereas A103 and T311 did so in 141 of 243 (58%) or 117 of 243 (48%) of the lesions. With regard to staining intensity of SM5-1, 157 of 243 (64%) showed a strong or very strong staining intensity, whereas A103 and T311 did so in 85 of 243 (35%) or 70 of 243 (29%) of the lesions. Staining intensity and percentage positivity correlated well for SM5-1, because from the 58 very strong positive metastases 55 showed staining in more than 75% of the cells within a lesion. Importantly, 52 of 56 MART-1-negative metastases and 81 of 89 Tyrosinase-negative metastases were positive for SM5-1. Thirty-eight metastases (15.6%) were negative for both A103 and T311. Of those, 35 (92.1%) were positive for SM5-1, demonstrating the value of SM5-1 in identifying melanoma-associated antigen-negative lesions. We conclude that SM5-1 could be of value in immunohistochemistry of melanoma.
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PMID:Differential expression of MART-1, tyrosinase, and SM5-1 in primary and metastatic melanoma. 1614 9

The aim of this study was to evaluate the role of tyrosinase mRNA appearance in blood of malignant melanoma (MM) patients, especially with advanced stages, for predicting the disease progression, and consequently the survival. The tyrosinase mRNA was measured by nested RT-PCR in peripheral venous blood samples obtained from 86 patients (53 male and 33 female) with mainly stage III and IV MM. The data were analyzed using standard methods for survival analysis and logistic regression. Tyrosinase was negative in the MM patients with the disease stage I or II, positive tyrosinase was in 11/50 patients with stage III and in 5/22 patients with stage IV. Systemic metastases developed in 14/16 patients with positive tyrosinase and in 41/70 with negative tyrosinase. The 3-year survival was 8% and 28% among the patients with positive and the patients with negative tyrosinase, respectively. The log rank test showed statistically significant better survival of tyrosinase negative patients when compared to tyrosinase positive patients (p=0.039). Multivariate analysis using logistic regression indicated tyrosinase to be a statistically significant prognostic factor for the survival of MM patients after controlling for Breslow and ulceration values (p=0.006). Positive tyrosinase in peripheral venous blood is statistically significant, and more importantly independent negative predictor of survival.
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PMID:Prognostic significance of tyrosinase mRNA detected by nested RT-PCR in patients with malignant melanoma. 1641 6

It is now established that sentinel node (SN) biopsy is a minimally-invasive procedure that accurately indicates the regional nodal status. In our institute, 14 consecutive patients had only one node micrometastases after elective lymph node dissection or positive SN for primary cutaneous melanoma. These 14 patients could be clearly divided into two groups: (i) patients who developed distant metastases or in-transit metastases (metastasized group); and (ii) and patients who remains free from metastases (non-metastasized group). The purpose of this study was to identify the histological and molecular factors that might predict the further dissemination beyond the SN. We assessed the maximum depth from the capsule to the deepest melanoma cells and the maximum diameter of melanoma nests in the lymph nodes as histological parameters and also evaluated the quantitative expression of tyrosinase mRNA as a molecular approach. The mean maximum depth and the maximum diameter were significantly smaller in the metastasized group than those in the non-metastasized group. Tyrosinase mRNA expression was strongly correlated with the histological tumor burden. Tyrosinase mRNA expression was higher in the former group than that in the latter group but there were no significant differences between them. Melanoma patients with small micrometastases (<0.5 mm deep, <1 mm in diameter) and a low level of tyrosinase mRNA had less chances for hematogenous metastases via lymph nodes.
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PMID:Prediction of metastases in melanoma patients with positive sentinel node: histological and molecular approach. 1720 98

Perivascular epithelioid cell tumor (PEComa) is rare entity and has been described only recently. By immunohistochemistry and genetics it belongs to the family of tumours which comprises angiomyolipoma, clear cell "sugar" tumor of lung, lymphangioleiomyomatosis and clear cell myomelanotic tumor of ligamentum falciforme/teres hepatis. We describe an unusual case of hepatic PEComa arising in a 55-year-old woman with previous history of glioblastoma. Histologically the tumor grew in expansive way, and was composed of clear and eosinophilic epithelioid cels, without vascular or lipomatous component characteristic of angiomyolipoma. There was mild nuclear pleomorphism, sporadic mitotic activity and haemorrhage without necrosis. On immunohistochemistry, the tumor was HMB-45+50, Melan-A and smooth muscle actin positive. Tyrosinase, S-100 protein, cytokeratin coctail, EMA, vimentin, muscle specific actin, CD10, TTF-1, hepatocyte, desmin and cyclin D1 were negative. Sporadic nuclear p53 positivity was seen. The main differential diagnosis of hepatic PEComa includes clear cell variant of liver cell adenoma and hepatocellular carcinoma, metastases of various clear cell carcinomas and metastasis of malignant melanoma. In respect of uncertain biologic potential of PEComa, long term follow up is indicated.
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PMID:[Perivascular epithelioid cell tumor (PEComa) of the liver: a case report and review of the literature]. 1737 Apr 72

The relationship between the disease course and the prognostic relevance of sequential tyrosinase reverse transcription-PCR assay in the peripheral blood of advanced metastatic melanoma patients was ascertained. The clinical usefulness of tyrosinase in stage IV melanoma patients is still debated, owing to the wide range of variability (positive expression from 30 up to 100% of patients) and the possibility of a transient shedding of melanoma cells into the bloodstream. A total of 200 consecutive stage IV metastatic patients treated at our department were included, 149 with active metastatic disease undergoing systemic therapies (group A), and 51 disease free after surgery (group B). For each patient, a baseline sample was obtained within 3 weeks of either the clinical/radiological demonstration of metastatic disease or the surgical treatment; thereafter, tyrosinase determinations were performed at day 1 of each therapy course before chemotherapy administration or at each follow-up visit. Tyrosinase expression was determined using standard reverse transcription-PCR nested techniques. A baseline positive determination was obtained in 72.5% of the patients with active metastatic disease (group A) but not in any of the patients who were disease free after surgery (group B). Therapy administration induced an early clearance of circulating melanoma cells, from 72.5 to 44.9% at the second down to 29.5% at the third determination. Tyrosinase expression before the third cycle was significantly associated with the clinical response: 56/81 (69.1%) patients with a negative tyrosinase determination obtained a response or a stable disease, whereas 29/34 (85.3%) patients with a positive test developed a progressive disease (P<0.001). A clinical response was observed in all the patients who had a negative tyrosinase at the first three determinations, although all patients whose first three determinations were positive developed a progressive disease. Multivariate analysis showed that baseline tyrosinase status carries an independent prognostic value on both overall survival and time to progression; moreover, tyrosinase results during follow-up were entered as time-dependent covariates in a multivariate analysis and were shown to be the most significant prognostic parameter associated to both overall survival and time to progression. In particular, the presence of a constant positive expression during follow-up was associated with the development of new metastatic sites in 95.6% of patients with active metastatic disease. Our results demonstrate that the discrepancies in the positive tyrosinase rates reported in the literature are related to the disease status at the time of sampling and to chemotherapy administration. Tyrosinase expression in the peripheral blood both at baseline and during follow-up can be considered a reliable prognostic parameter associated with the response to treatment, development of new metastatic sites, time to progression and survival.
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PMID:Prognostic relevance of baseline and sequential peripheral blood tyrosinase expression in 200 consecutive advanced metastatic melanoma patients. 1749 82

Personalized vaccine, recognized after the failure of allogenic melanoma whole cell and lysate vaccine phase III trials, involves culturing cells from a patient's own tumor within a short duration and with less passages but with optimized expression of tumor-associated antigens (TAAs). Its feasibility is established by comparing pure cell lines generated from fresh and cryopreserved tissues (n=164) of patients with lymph node (LN) and distant metastases. Stable cell lines (from 67% of specimens) are subcultured after cryopreserving them. Pure cell lines established after eliminating fibroblasts (from 96% of the cell lines) include those from LN (69%), soft tissues including cutaneous (60%), liver (64%), lung (75%), bone (80%), brain (75%), and other sites (73%). Within 3.5 months, stable cell lines (> or =50 million cells) are established from initiating the cell culture. For LN metastases, the duration differs significantly (P2<0.05) between fresh (1.4-3.4 months) and cryopreserved (2.4-4.7 months) tissues. The expression of TAAs varies as follows: Tyrosinase (81%) >Melan-A (80%) >HMB45/gp-100 (75%) >Mel-5/TRP-1 (65%) >MAGE-1 (47%) > S-100 (28%). The number of TAAs per cell line differs between early (<7) and late (>7) passages. Among late passage cell lines, lesser percentage of cell lines express three to six antigens pointing out that early passage (<7) cell lines may be needed for antigen-targeted immunotherapy. This study provides a protocol for establishing cell lines within 2-5 months for personalized vaccine therapy for nodal and organ metastatic melanoma patients.
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PMID:Establishment of stable cell lines for personalized melanoma cell vaccine. 2037 43


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