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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metastatic dormancy of melanoma has not received sufficient attention, most likely because once detectable, metastasis is almost invariably fatal and, understandably, the focus has been on finding ways to prolong life of patients with overt recurrences. Nevertheless, analysis of the published clinical and experimental data on melanoma indicates that some aspect of melanoma biology imitate traits recently associated with dormancy in other solid cancers. Among them the ability of some melanomas to disseminate early during primary tumor progression and once disseminated, to remain undetected (dormant) for years. Comparison of cutaneous and uveal melanoma indicates that, in spite of being of the same origin, they differ profoundly in their clinical progression. Importantly for this discussion, between 40 and 50% of uveal melanoma remain undetected for longer than a decade, while less than 5% of cutaneous melanoma show this behavior. Both types of melanoma have activating oncogene mutations that provide autonomous pro-proliferative signals, yet the consensus is that those are not sufficient for tumor progression. If that is the case, it is possible to envision that signals from outside the tumor cell, (microenvironment) shape the fate of an individual disseminated cell, regardless of an oncogene mutation, to progress or to pause in a state of dormancy. To stimulate further debate and inquiry we describe here a few examples of potential signals that might modify the fate of disseminated cell and provide brief description of the current knowledge on dormancy in other cancers. Our hope is to convince the reader that disseminated melanoma cells do enter periods of prolonged dormancy and that finding ways to induce it, or to prolong it, might mean an extension of symptoms-free life for melanoma patients. Ultimately, understanding the biology of dormancy and the mechanisms of dormant cell survival, might allow for their specific targeting and elimination.
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PMID:Dormancy of metastatic melanoma. 1984 43

Cutaneous malignant melanoma represents one of the most dramatic skin cancers because its incidence is steadily growing in White populations. Of note, its metastatic risk and mortality dramatically increase when the primary neoplasm reaches about one millimeter thick. It is believed that angiogenesis and lymphangiogenesis associated with cutaneous melanoma potentially influence the neoplastic progression of the primary tumor and its metastases. In some instances, both the intratumoral and peritumoral microvasculature are correlated to booming of the tumoral growth fraction. In addition, the vascular network serves as a migration path for the intravascular and perivascular neoplastic spread. Hence, the quantification of the microvasculature might help establishing a prognostic factor of evolution. Among the available methods, spectral analysis of immunohistochemical sections highlighting vessels helps defining the microvasculature distribution. The benefit of using spectral analysis is discussed and the modalities of application of this analytical method are scrutinized.
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PMID:[Spectral analysis of the microvasculature of primary cutaneous melanoma]. 2016 38

Lymphocytic infiltration of primary cutaneous melanoma has been demonstrated to be of prognostic significance. Tumor infiltrating lymphocytes (TILs) were evaluated on histologic sections of pT4 primary cutaneous melanoma from 293 patients, accrued in protocols 1690 and 1694 of the Eastern Cooperative Oncology Group. Data for the 60-month follow-up were available. Statistical analysis of the pathologic data evaluated the correlation of regional lymph node metastasis and response to interferon therapy, overall survival, and relapse-free survival. In multivariate analysis, there was significant correlation of the presence of TILs and improved survival. The presence of TILs did not affect the survival of patients treated with interferon alfa-2b. Presence of a localized dominant tumor nodule within the primary tumor had an adverse effect on relapse-free survival (P = .044) that was also marginally present for overall survival (P = .112). The presence of TILs has prognostic but not predictive value, and the presence of a dominant nodule in the primary lesion represents a new adverse prognostic factor that should be incorporated in the evaluation of primary melanoma. This study confirmed the importance of tumor ulceration and the number of positive lymph nodes on outcome.
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PMID:Presence of tumor-infiltrating lymphocytes and a dominant nodule within primary melanoma are prognostic factors for relapse-free survival of patients with thick (t4) primary melanoma: pathologic analysis of the e1690 and e1694 intergroup trials. 2023 18

Although risk factors for primary cutaneous melanoma are well defined, relatively little is known about predictors for second primary melanoma. Given the rising incidence of this cancer, coupled with improvements in survival, there is a prevalent and growing pool of patients at risk of second primary melanomas. To identify the predictors of second primary melanoma, we followed a cohort of 1,083 Queensland patients diagnosed with incident melanoma between 1982 and 1990 and who completed a baseline questionnaire. During a median follow-up of 16.5 years, 221 patients were diagnosed with at least one additional primary melanoma. In multivariate analyses, second primary melanomas were associated with high nevus count (hazard ratio (HR), 2.91; 95% confidence interval (CI) 1.94-4.35), high familial melanoma risk (HR, 2.12; 95% CI 1.34-3.36), fair skin (HR, 1.51; 95% CI 1.06-2.16), inability to tan (HR, 1.66; 95% CI 1.13-2.43), an in situ first primary melanoma (HR, 1.36; 95% CI 0.99-1.87), and male sex (HR, 1.49; 95% CI 1.12-2.00). Patients whose first primary was lentigo maligna melanoma (HR, 1.80; 95% CI 1.05-3.07) or nodular melanoma (HR, 2.13; 95% CI 1.21-3.74) had higher risks of subsequent primaries than patients whose first primary tumor was superficial spreading melanoma. These characteristics could be assessed in patients presenting with first primary melanoma to evaluate risk of developing a second primary.
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PMID:Nevi, family history, and fair skin increase the risk of second primary melanoma. 2094 47

The surgical management of primary cutaneous melanoma, from the diagnostic biopsy through the wide local excision and nodal staging, must be carefully planned, and the biology of the melanoma, microstaging and primary tumor pathologic features of the melanoma, location on the body, patient preferences, and comorbidities must be considered. The treating surgeon must balance preservation of oncologic principles, with optimization of functional and aesthetic outcome. This article reviews the rationale behind the surgical approach in the patient with a primary melanoma.
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PMID:Surgical approach to primary cutaneous melanoma. 2111 58

Changes in the 2010 American Joint Commission on Cancer melanoma staging guidelines include the evaluation of primary tumor mitotic index (mitogenicity) and the recognized prognostic significance of a single melanoma cell in a sentinel lymph node. These revised criteria have important practice implications for dermatopathologists as well as for dermatologists, oncologists and surgeons who treat patients with cutaneous melanoma.
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PMID:AJCC melanoma staging update: impact on dermatopathology practice and patient management. 2138 99

The reported frequencies of germline mutations in the melanoma candidate genes are low in patients with uveal melanoma (UM). However, the number of families studied is limited and the majority of the published reports used low-sensitivity techniques for mutational screening. Identifying the frequency of alterations in any of the melanoma genes in patients with UM with increased hereditary cancer risk is important for proper counseling of these patients. We studied a total of 47 patients with UM including three with a family history of UM, 18 with a family and/or personal history of cutaneous melanoma (CM), three with early age at diagnosis (<30), 11 with increased risk for a known familial cancer syndrome, and 12 with a second primary tumor. Germline screening for mutations in CDKN2A, p14ARF, and exon 2 of CDK4 was carried out by direct sequencing. We identified a variant (IVS1-69 C>T) of uncertain significance in exon 1b of p14ARF in one of the patients with UM and his mother who also had UM. The variant was neither detected in any of the other patients with UM nor in 146 controls. We did not identify pathogenic mutations in CDKN2A nor exon 2 of CDK4 gene. Our study supports the low frequency of germline mutation of the CM candidate genes in patients with UM with family histories suggestive of a high risk for hereditary cancer. Germline testing for CDKN2A might be reserved for patients with UM with a family history of two or more CM.
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PMID:Melanoma candidate genes CDKN2A/p16/INK4A, p14ARF, and CDK4 sequencing in patients with uveal melanoma with relative high-risk for hereditary cancer predisposition. 2141 76

Metastasis of tumor cells to distant organs is the leading cause of death in melanoma. Yet, the mechanisms of metastasis remain poorly understood. One key question is whether all cells in a primary tumor are equally likely to metastasize or whether subpopulations of cells preferentially give rise to metastases. Here, we identified a subpopulation of uveal melanoma cells expressing the multidrug resistance transporter ABCB1 that are highly metastatic compared to ABCB1(-) bulk tumor cells. ABCB1(+) cells also exhibited enhanced clonogenicity, anchorage-independent growth, tumorigenicity and mitochondrial activity compared to ABCB1(-) cells. A375 cutaneous melanoma cells contained a similar subpopulation of highly metastatic ABCB1(+) cells. These findings suggest that some uveal melanoma cells have greater potential for metastasis than others and that a better understanding of such cells may be necessary for more successful therapies for metastatic melanoma.
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PMID:ABCB1 identifies a subpopulation of uveal melanoma cells with high metastatic propensity. 2157 42

Complete surgical excision at an early stage remains the only curative treatment for cutaneous melanoma with few available adjuvant therapy options. Nevertheless, melanoma is a relatively immunogenic tumor type and particularly amenable to immunotherapeutic approaches. A dense network of cutaneous dendritic cells (DC) may account for the reported efficacy of vaccination through the skin and provide an attractive target for the immunotherapy of melanoma. Several phenotypically distinct DC subsets are discernable in the skin, among others, epidermal Langerhans cells and dermal DC. Upon appropriate activation both subsets can efficiently migrate to melanoma-draining lymph nodes (LN) to prime T cell-mediated responses. Unfortunately, from an early stage, melanoma development is characterized by strong immune suppression, facilitating unchecked tumor growth and spread. Particularly the primary tumor site and the first-line tumor-draining LN, the so-called sentinel LN, bear the brunt of this melanoma-induced immune suppression-and these are exactly the sites where anti-melanoma effector T cell responses should be primed by DC in order to prevent early metastasis. Through local immunopotentiation or through DC-targeted vaccination, the dermis may be utilized as a portal to activate DC and kick-start or boost effective T cell-mediated anti-melanoma immunity, even in the face of this immune suppression.
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PMID:The dermis as a portal for dendritic cell-targeted immunotherapy of cutaneous melanoma. 2168 85

Several germline mutations and sequence variants in cancer predisposition genes have been described. Among these, the CDKN2A p.A148T variant appears to be frequent in patients with melanoma, at least in certain ethnic groups. In this case-control study, we evaluated 127 patients with cutaneous melanoma and 128 controls from Southern Brazil, the region with the highest melanoma incidence rates in the country. Using PCR-RFLP, we demonstrate that CDKN2A p.A148T variant was significantly more frequent in patients with melanoma than in controls (12.6% vs 3.9%; P=0.009). There was no association between presence of the polymorphism and tumor thickness, site of the primary tumor, melanoma subtype, age at diagnosis, quantitative and qualitative number of nevi. Patients with a positive family of history for other cancers were particularly prone to carry the CDKN2A p.A148T allele. All patients with p.A148T-positive melanoma reported European ancestry, especially German, and this was confirmed using a panel of ancestry-informative INDELs. Our data suggest that CDKN2A p.A148T is a melanoma susceptibility allele in Southern Brazil and is particularly common in patients with melanoma of predominantly European ancestry.
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PMID:The CDKN2A p.A148T variant is associated with cutaneous melanoma in Southern Brazil. 2189 73


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