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)

The use of tyrosinase-based polymerase chain reaction (PCR) tests for the detection of circulating tumour cells in the blood of melanoma patients has led to highly controversial results. We here report on the analysis of 120 blood samples from 76 stage I to IV melanoma patients using a new MART-1/Melan-A PCR system in conjunction with the tyrosinase-specific assay reported in the literature. While there were no positive results in localized disease (stages I and II), identification of specific PCR products in stage III melanoma patients was restricted to the MART-1/Melan-A tests, with positive results in 11% (two out of 19) of the blood specimens analysed. Stage IV melanoma patients presented with the highest incidence of detectable mRNA levels, with positive results for tyrosinase in 38% (12 out of 32) and for MART-1/Melan-A in 22% (seven out of 32). By delineating 64 follow-up specimens covering sampling periods of up to 33 weeks, stable mRNA expression profiles were identified in nearly 95%. Four patients, however, showed PCR changes towards positive MART-1/Melan-A expression that were linked to metastatic melanoma progression. Taken together, PCR tests for tyrosinase and MART-1/Melan-A seem to lack sufficient detection frequencies for the routine monitoring of melanoma disease. Regarding the link between MART-1/Melan-A seroconversion and the development of metastatic disease, further studies are needed to clarify the clinical value of this observation.
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PMID:MART-1/Melan-A and tyrosinase transcripts in peripheral blood of melanoma patients: PCR analyses and follow-up testing in relation to clinical stage and disease progression. 1159 94

We report here on 2 patients who received adjuvant vaccination with an HLA-A2- or HLA-A24-restricted tyrosinase peptide, respectively, and GM-CSF for frequently relapsing stage IV melanoma. Following resection of metastases and irradiation of brain metastases in 1 patient, both patients were without evidence of disease when receiving the first vaccination. While the patients had had 9 and 12, respectively, mostly s.c., relapses during the 3 years before vaccination, they experienced freedom from relapse for more than 2 years after vaccination. We found a T-cell response to the vaccine peptide in both patients in the peripheral blood by ex vivo IFN-gamma ELISPOT assay. The T-cell population could be further characterized by 4-color flow cytometry in 1 patient, showing that the majority of the peptide-specific CD3(+)CD8(+)IFN-gamma(+) T cells were granzyme B-positive and CCR-7-negative, characterizing them as effector T cells with the ability to mediate cytotoxicity and migrate to inflamed tissues. In this patient also, augmentation of the T-cell response to autologous tumor cells by vaccination could be detected. A single-site postvaccination relapse occurred in both patients, showing downregulation of tyrosinase expression in 1 patient, while normal expression levels for tyrosinase, MHC class I antigens and components of the antigen-processing machinery were found in the other patient. These results suggest that peptide vaccination resulted in a prolonged relapse-free interval in these high-risk patients.
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PMID:Long-term freedom from recurrence in 2 stage IV melanoma patients following vaccination with tyrosinase peptides. 1199 9

Vascular endothelial growth factor (VEGF) is known to play a crucial role in the growth and metastatization of solid tumours. In cancer patients, high VEGF serum levels correlate with tumour status and prognosis, but to date few data have been reported concerning VEGF in melanoma patients. In the present study, immunoenzymatic and reverse transcription-polymerase chain reaction (RT-PCR) techniques were used to detect VEGF-165 serum levels and the presence of tyrosinase mRNA, respectively, in the peripheral blood of a cohort of 155 melanoma patients at different clinical stages (30 stage I, 40 stage II, 40 stage III and 45 stage IV; AJCC classification). Data were compared with both the extent of the disease and the clinical course. The aim was to assess the relationship between VEGF serum levels, the presence of detectable circulating melanoma cells and melanoma progression. A significant increase in VEGF serum levels was found in melanoma patients, in particular in those with metastatic disease; a higher incidence of relapses was found in stage I-III disease-free patients who showed an increase in VEGF during follow-up. VEGF serum levels were significantly higher in patients with detectable circulating melanoma cells than in those with negative tyrosinase mRNA expression. The finding of both an increase in VEGF and the presence of detectable melanoma cells during follow-up was associated with a relapse rate of 81%. The relapse rate was significantly lower when either of the two parameters were present separately. Multivariate analysis of both overall survival and time-to-progression selected baseline tyrosinase expression in peripheral blood but not VEGF serum levels as an independent prognostic factor.
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PMID:VEGF-165 serum levels and tyrosinase expression in melanoma patients: correlation with the clinical course. 1217 Jan 81

Sentinel lymph node (SLN) analysis allows the detection of occult metastases in patients with melanoma. The use of serial sections and immunohistochemical investigations (ICH) increases the chance of identifying metastases. Nevertheless, detection of mRNA of the tyrosinase gene through reverse transcription-polymerase chain reaction (RT-PCR) is the most sensitive tool for detection of occult melanoma cells in SLN. From September 1999 to August 2001, in the Anatomic Pathology Unit of M. Bufalini Hospital of Cesena, 489 SLNs from 332 patients with primary melanoma in clinical stages I and II (according to AJCC) were examined. There were 66 (13.5%) SLNs and 58 (17.4%) cases with metastasis revealed by histology and ICH. A single case with metastatic SLN was found in patients with melanomas < or = 1 mm in thickness. The percentage of cases with metastases in SLN correlated with thickness of the primary melanoma (p < 0.0001). RT-PCR for tyrosinase was carried out in 448 SLNs from of 308 cases. Overall, the RT-PCR results were positive in 149 (48.4%) patients and in 169 SLNs (37.9%). RT-PCR results showed a strong positive correlation with tumor thickness of primary melanoma (p < 0.0001) and with the clinical stage (p < 0.0001). Of the RT-PCR-positive cases, 18 showed intracapsular aggregates of nevus cells. Besides the percentage of positive cases, once those with nevus aggregates were excluded, overall, the RT-PCR revealed the presence of tyrosinase mRNA in 34.5% of patients with negative histology and ICH. Ongoing monitoring is necessary to define the real prognostic implication of the presumed presence of occult melanoma deposits disclosed by RT-PCR in SLNs.
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PMID:[The sentinel lymph node in melanoma: utilization of molecular biology (RT-PCR) to detect occult metastases]. 1232 17

Nodal nevi represent a potential diagnostic pitfall in the analysis of lymph nodes. They may be confused with metastatic melanoma or carcinoma. Although several morphologic guidelines exist for the recognition of nodal nevi, on occasion immunohistochemical studies may be helpful for diagnosis, especially when melanocytes extend into the lymph node parenchyma. To learn more about the immunohistochemical profile of nodal nevi we examined 15 nodal nevi for the expression of S-100 protein, gp100 (HMB-45), Melan-A/MART-1 (A103), and tyrosinase (T311), and we studied the expression of Ki-67 (MIB-1) in nodal nevi and 40 melanoma metastases (35 lymph node and five cutaneous metastases). All nodal nevi were homogeneously immunoreactive for S-100 protein, tyrosinase, and Melan-A/MART-1. Two nodal nevi were focally positive for gp100. Fourteen of 15 nodal nevi were completely negative for Ki-67. One large cellular nodal nevus showed nuclear labeling in <0.2% of melanocytes. All metastases showed MIB-1 labeling. However, the percentage of labeled tumor cells varied widely, ranging from 2% to 80%. These results demonstrate that MIB-1 and HMB-45 are helpful reagents for the distinction of nodal nevi from melanoma. Immunohistochemistry for S-100 protein, Melan-A/MART-1, or tyrosinase facilitates the recognition of melanocytes but does not distinguish between nodal nevus and metastatic melanoma.
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PMID:Expression of melanocyte differentiation antigens and ki-67 in nodal nevi and comparison of ki-67 expression with metastatic melanoma. 1236 50

Malignant melanomas of the vagina are rare tumors. In this study we present the clinicopathologic features and immunohistochemical analysis of 26 such cases seen in our institution over a period of 30 years. The patients' age ranged from 38 to 90 years (mean 60 years); three patients were premenopausal. Ethnicity was known in 24 patients: 20 white, 2 hispanic, 1 black, and 1 Asian. The most common presenting symptom was vaginal bleeding, followed by vaginal mass. Grossly, the tumor was polypoid-nodular in the majority of cases. The neoplastic cells were epithelioid in 15 cases and spindled in three cases; eight cases had both cell types. Vascular-lymphatic invasion was seen in six cases and perineural invasion was seen in four cases. S-100 was strongly and diffusely positive in 25 of 26 cases (96%). HMB-45 was strongly positive in 16 (62%), 3 (11%) were focally positive, 1 case showed a rare positive cell, and 6 (23%) were negative. With MART-1, 20 cases (77%) were strongly positive, 1 (4%) showed a rare weakly positive cell, and 5 (19%) were negative. Twenty-one cases (81%) expressed tyrosinase and 20 (77%) expressed microphthalmia transcription factor. Twenty cases were Chung's level IV, 3 were level III, and 2 were level II. The patients were treated as follows: anterior exenteration with or without lymph node dissection and with or without radiotherapy (RT) or chemotherapy (CT) (7 cases), wide local excision with or without lymph node dissection and RT/CT (10 cases), hysterectomy with vaginectomy with or without RT/CT (3 cases), vaginectomy with RT (1 case), RT (1 case), and RT and CT (1 case). One patient had palliative RT for the brain metastasis only. Follow-up was available in 23 patients ranging from 3 to 276 months (median 18 months). Local recurrence after primary treatment was seen in six patients and distant metastases in 11 patients. Fifteen patients died of the disease (3-83 months), 4 have no evidence of disease (5-24 months), and 4 are alive with disease (6-276 months). This study confirms the poor prognosis of patients with vaginal melanoma. S-100 remains the most sensitive marker for these tumors. HMB-45 is negative in 23% cases of vaginal melanoma. Tyrosinase and MART-1 are useful markers when S-100 is negative or only focally positive.
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PMID:Vaginal melanoma: a clinicopathologic and immunohistochemical study of 26 cases. 1240 21

Circulating malignant cells in peripheral blood are thought to be precursors and surrogate markers of distant metastases and hence markers of a poor clinical outcome. In this study, we used the detection of MART-1 and tyrosinase (TYR) mRNA with a quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay to identify circulating melanoma cells. Blood samples were obtained from 35 patients with metastatic melanoma before, during and after treatment with interleukin-2, interferon-alpha and cisplatin. In addition, MART-1 and TYR protein was identified by immunohistochemistry in consecutive biopsies from 15 of the patients. Analysis of three daily blood samples for 3 days demonstrated that four out of 11 patients examined were negative for both markers on all occasions, and two patients were positive for both markers on all occasions but one. The remaining five patients showed sporadic low positive results for one or the other of the two markers. By comparing the immunohistochemistry results from consecutive biopsies with the RT-PCR results, we demonstrated that patients with MART-1 and TYR protein in their tumour cells had circulating MART-1 and TYR mRNA in 77% and 54% of the cases, respectively. During treatment, the majority of patients who were positive for MART-1 and TYR mRNA converted to being negative. However, these conversions did not significantly correlate with objective response. The presence of TYR mRNA in one of the first two samples showed a trend towards being an independent prognostic factor for poor survival.
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PMID:Quantitative RT-PCR assessment of melanoma cells in peripheral blood during immunotherapy for metastatic melanoma. 1245 48

Cutaneous melanomas have been found to express several immunogenic differentiation melanoma-associated antigens (MAAs) that have been suggested to play an important role in disease outcome. Adaptive host immunity to MAAs has shown some level of control on melanoma progression. To date, there has been no definitive report correlating the level of differentiated MAAs gene expression in melanomas with overall disease outcome. Metastasis of melanoma to distant visceral organ sites usually indicates a survival of less than 1 year; however, a subset of patients who undergo cytoreductive surgery of distant metastases survive for a longer period. We hypothesized that the gene expression level of differentiation MAAs in metastatic melanoma (AJCC stage IV) lesions would be predictive of survival. We focused on three known differentiation MAAs: tyrosinase (TYR), TYR-related protein 2 (TRP-2), and melanoma antigen recognized by T cells 1 (MART-1); all three of them are known to induce immune responses in melanoma patients and are frequently expressed in melanomas. A quantitative reverse-transcriptase RealTime PCR (qRT) assay was developed for these MAAs to assess mRNA expression in metastatic melanoma tumors obtained from cytoreductive surgery of AJCC stage IV melanoma patients (n = 35). Patients were followed up for over 60 months. There was a variation in mRNA copy levels for individual MAAs in melanoma tumors. Elevated MAA mRNA copy levels of TYR and TRP-2 significantly (P < 0.03 and < 0.009, respectively) correlated with improved overall survival. Patients having at least one MAA expressed in their tumors had a significantly (P = 0.01) better overall survival (median 16 months). These studies demonstrate that levels of differentiated MAA mRNA expression of advanced-stage metastatic melanomas can be used as molecular predictive factors of disease outcome. The studies also imply that an assessment of melanoma tumor MAAs may provide a stratification factor targeted for active-specific immunotherapy.
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PMID:Expression of differentiation melanoma-associated antigen genes is associated with favorable disease outcome in advanced-stage melanomas. 1254

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

Primary sinonasal tract mucosal malignant melanomas are uncommon tumors that are frequently misclassified, resulting in inappropriate clinical management. A total of 115 cases of sinonasal tract mucosal malignant melanoma included 59 females and 56 males, 13-93 years of age (mean 64.3 years). Patients presented most frequently with epistaxis (n = 52), mass (n = 42), and/or nasal obstruction (n = 34) present for a mean of 8.2 months. The majority of tumors involved the nasal cavity (n = 34), septum alone, or a combination of the nasal cavity and sinuses (n = 39) with a mean size of 2.4 cm. Histologically, the tumors were composed of a variety of cell types (epithelioid, spindled, undifferentiated), frequently arranged in a peritheliomatous distribution (n = 39). Immunohistochemical studies confirmed the diagnosis of sinonasal tract mucosal malignant melanomas with positive reactions for S-100 protein, tyrosinase, HMB-45, melan A, and microphthalmia transcription factor. Sinonasal tract mucosal malignant melanomas need to be considered in the differential diagnosis of most sinonasal malignancies, particularly carcinoma, lymphoma, sarcoma, and olfactory neuroblastoma. Surgery accompanied by radiation and/or chemotherapy was generally used. The majority of patients developed a recurrence (n = 79), with 75 patients dying with disseminated disease (mean 2.3 years), whereas 40 patients are either alive or had died of unrelated causes (mean 13.9 years). A TNM-type classification separated by anatomic site of involvement and metastatic disease is proposed to predict biologic behavior.
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PMID:Sinonasal tract and nasopharyngeal melanomas: a clinicopathologic study of 115 cases with a proposed staging system. 1271 45


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