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

Tumors often display unrestricted cell cycling attributable to a dysfunctional G(1)-S checkpoint. One of the mechanisms leading to such a defect is the inactivation of the cyclin-dependent kinase inhibitor p16(INK4a). Although inactivation of p16(INK4a) is observed in a wide range of tumors, including cutaneous melanoma, genetic alteration of p16(INK4a) is reportedly uncommon in uveal melanoma. Here we show that the p16(INK4a) promoter is hypermethylated in 6 of 12 uveal melanoma cell lines and in 7 of 22 primary uveal melanomas analyzed. Five of seven patients with a methylated primary tumor died of metastatic disease compared with 2 of 15 patients with a nonmethylated primary tumor. We also show that all uveal melanoma cell lines with a hypermethylated p16(INK4a) promoter have lost p16(INK4a) expression but have maintained the expression of p14(ARF). Treatment of uveal melanoma cell lines with 5-aza-2'-deoxycytidine results in demethylation of p16(INK4a) and in reexpression of p16(INK4a) mRNA, which is maintained upon withdrawal of the 5-aza-2'-deoxycytidine. In conclusion, p16(INK4a) promoter methylation appears to be a common event in uveal melanoma and is accompanied by the loss of p16(INK4a) expression.
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PMID:Promoter hypermethylation: a common cause of reduced p16(INK4a) expression in uveal melanoma. 1143 74

The American Joint Committee on Cancer (AJCC) recently launched a new staging system for cutaneous melanoma that was based on clinical experience with a large number of patients treated in major centers worldwide. As this system includes various histopathologic parameters of the primary melanoma and of melanoma metastasis, including micrometastases in the sentinel lymph node (SLN), they are discussed here. Special attention is given to ulceration of the primary tumor, because it remains a dominant prognostic parameter in addition to tumor thickness. Molecular markers that may reflect aggressive behavior of the primary melanoma also are described. Finally, pathologic examination of SLNs is addressed with emphasis on the efficacy of various microstaging approaches.
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PMID:Pathologic staging of melanoma. 1217 Apr 40

Surgical interventions have important role in the treatment of all stages of malignant melanoma. Surgery is the primary treatment of localized cutaneous melanoma. Excision of the primary tumor makes it possible to set up the histological diagnosis and to determine pathological prognostic factors. Appropriate surgical margin is important for local disease control. Sentinel lymph node biopsy with detailed histological examination has gained prominent importance for correct histological staging and for determining adjuvant oncological treatment. Surgery is the primary treatment of isolated regional metastases. Surgical methods also have a role in the palliative management of distant metastatic melanoma. In the present review the most important issues of the surgical treatment of malignant melanoma have been discussed in detail.
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PMID:[The role of surgery in the treatment of malignant melanoma]. 1270 58

The incidence of primary cutaneous melanoma continues to increase and is a growing public health problem. By virtue of its metastatic potential, melanoma accounts for most of the deaths from cutaneous malignancies. Management of cutaneous melanoma has undergone a paradigm shift in recent years. Clinical studies have furthered our understanding of the biology of this disease and have changed the standards of care. Specifically, sentinel node biopsy and interferon as the first effective postsurgical therapy have had a significant impact on the treatment of patients with melanoma. Surgery remains the primary treatment modality for cutaneous melanoma. An adequate excision of the primary lesion accomplishes durable local control and is curative for patients without micrometastatic disease. Although the extent of surgical resection has decreased in recent years, the standard treatment for primary cutaneous melanoma remains wide surgical excision with histologically negative margins. The extent of excision is based on the theory that the incidence and radial extent of local recurrences can be predicted by specific primary tumor histopathologic characteristics. Tumor thickness and ulceration are the most important histologic features associated with prognosis and are the basis for the current recommendations for surgical treatment of the primary tumor. The extent of surgical therapy for primary melanoma is an area of ongoing debate. No clinical trial has shown a survival disadvantage for narrow versus wide excision regimens for melanoma of any thickness. Ongoing clinical trials will determine the relationship between the extent of surgical therapy for the primary tumor and the outcomes of recurrence and survival in patients with melanoma.
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PMID:Primary cutaneous melanoma: surgical management and other treatment options. 1271 95

Data from the Hawaii Tumor Registry suggest that the incidence of melanoma in the non-Caucasian population of Hawaii is not substantially different from that of the remainder of the United States. Our experience indicates that melanoma in this population, although unusual, is not rare. Although lesions on the palms and soles are more common. as are subungal melanomas, primary tumors on other skin sites account for the majority of patients with cutaneous melanoma in the non-Caucasian population. The substantial difference in primary tumor thickness suggests the reported poorer outcomes for non-Caucasian patients with cutaneous melanoma may be explained, at least in part, by a delay in diagnosis. Given the evidence that preventive measures and educational efforts have dramatically impacted the diagnosis and outcome of melanoma patients, it is critical to recognize that similar efforts should be directed at the non-Caucasian population.
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PMID:Malignant melanoma in non-Caucasians: experience from Hawaii. 1274 10

Our aim was to evaluate whether the number of circulating lymphocytes expressing costimulatory molecules can be associated with melanoma prognosis. We determined the concentration of peripheral blood lymphocytes, which expressed the CD80/CD86 or CD28/CTLA-4 molecules, in 38 patients with cutaneous melanoma and 27 controls. The number of each cell subset was compared between patients and controls, as well as between groups of patients stratified according to Breslow thickness of the primary tumor (< or = 2 mm vs > 2 mm) or to survival after 3 years. The concentration of circulating lymphocytes expressing the CD80/CD86 molecules was not significantly different between patients and controls. There was a lower number of CD3(+)CD8(+)CD28(+) cells, as well as a higher CD3(+)CD8(+)/CD3(+)CD8(+)CD28(+) cell ratio, in melanoma patients than in controls. Melanoma patients with thinner tumors and those surviving revealed an increase of CD19(+)CD80(+) and CD19(+)CD80(+)CD86(+) cells, as well as a higher concentration of CD3(+)CD4(+)CD28(+) cells. CD80(+) B cells and a low CD8 suppressor/cytolytic cell ratio correlate with a good prognosis in melanoma. Our findings support our conclusion that CD80(+) B cells may be important antigen presenting cells that can contribute to an antimelanoma immune response and are candidates to be monitored in melanoma patients.
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PMID:Changes in the number of CD80(+), CD86(+), and CD28(+) peripheral blood lymphocytes have prognostic value in melanoma patients. 1287 58

We have previously reported a high prevalence of hypothyroidism among patients with uveal melanoma. The objectives of the present study were to determine if a similar pattern of thyroid pathology exists among patients with cutaneous melanoma as well. To address this question, the medical records of all patients registered at the University of Texas M.D. Anderson Cancer Center with a diagnosis of cutaneous melanoma during the years 1997 and 1998 were examined for a history of overt hypothyroidism, defined as a requirement for thyroid hormone replacement. Data regarding stage and site of the primary tumor were obtained for these patients and for age/gender matched euthyroid controls from the same melanoma study population. Among 1,580 cutaneous melanoma patients (948 M/632 F), 111 (7.0%) gave a history of hypothyroidism [23/948 M (2.4%) and 88/632 F (13.9%)]. The prevalences of hypothyroidism for both males and females were significantly higher than those reported for the general population. Characteristics of the primary tumor did not differ between cases and controls, although there was a trend for a lower rate of primary tumor ulceration among the hypothyroid case subjects. We conclude that hypothyroidism of varied etiologies is common among patients with cutaneous melanoma. These data suggest that melanoma may be responsive to hormones of the thyroid hormone control loop, raising many questions of clinical and biologic importance.
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PMID:High prevalence of hypothyroidism among patients with cutaneous melanoma. 1288

Early stage primary human cutaneous melanoma is known to remain relatively avascular and dormant for up to a decade, after which it may give rise to more rapidly growing, vascular and metastatically- competent primary tumor. Clinical dormancy of early stage human melanomas can be recapitulated experimentally by injection of cell lines established from such tumors into nude mice. For example, WM1341B cells, which were isolated from a thin vertical growth phase (VGP) human melanoma, are non-tumorigenic in nude mice even though some of the cells remain viable for at least three weeks at the site of orthotopic injection. These cells produce little or no vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), a potent stimulator of angiogenesis. In order to determine whether their in vivo dormant behaviour may therefore be related to an inability to induce tumor angiogenesis, subpopulations of WM1341B cells were engineered to constitutively overexpress the VEGF/VPF121 isoform. This apparently single modification was sufficient to induce overt and progressively growing tumors by several independent VEGF/VPF121 producing clones, which could be largely blocked by systemic treatment of mice with a monoclonal anti-VEGF neutralizing antibody (A 4.6.1). No evidence for an autocrine mechanism of growth stimulation by VEGF was found. Taken together, these results support the notion that defective angiogenesis may, at least in part, account for dormant phenotype of some early stage primary melanomas. Since the induction of an overt tumorigenic phenotype in several VEGF/VPF transfected WM1341B clones appears to depend exclusively on their expression of VEGF/VPF, such sublines should be useful for screening the activity of known or potential VEGF/VPF ligand or VEGF/VPF receptor antagonists in an in vivo context.
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PMID:The dormant in vivo phenotype of early stage primary human melanoma: termination by overexpression of vascular endothelial growth factor. 1451 61

In 2002, the American Joint Committee on Cancer (AJCC) revised the staging system for cutaneous melanoma on the basis of a survival analysis of important melanoma prognostic factors. Features of the revised system include new strata for primary tumor thickness, incorporation of primary tumor ulceration as an important staging criterion in both the tumor (T) and node (N) classifications, revision of the N classification to reflect the prognostic significance of regional nodal tumor burden, and new categories for distant metastatic disease. These changes reflect evolving insight into melanoma arising from the results of numerous clinical investigations and database analyses. One of the most important recent changes in melanoma care is the establishment of lymphatic mapping and sentinel lymph node (SLN) biopsy as a highly accurate and minimally morbid technique for pathologic regional nodal staging. In this article, the salient features of the revised melanoma staging system are examined, with specific attention paid to its use in this era of lymphatic mapping and SLN biopsy.
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PMID:The new staging system for cutaneous melanoma in the era of lymphatic mapping. 1519 May

The natural course of cutaneous melanoma (CM) is determined by its metastatic spread and depends on tumor thickness, ulceration, gender, localization, and the histologic subtype of the primary tumor. CM metastasis develops via three main metastatic pathways and occurs as satellite or in-transit metastasis, as regional lymph node metastasis or as distant metastasis at the time of primary recurrence. About 50% of all CM patients with tumor progression firstly develop regional lymph node metastases. In the other 50% the first metastases are satellite or in-transit metastases (about 20%), or immediately distant metastases (about 30%). Development of distant metastasis appears to be an early event in metastatic spread and may in the majority of cases originate from the primary tumor, only few cases may develop secondarily to locoregional metastasis. Reporting of organ involvement in distant metastasis greatly differs between the results of imaging techniques and autopsy results in respect to the metastatic patterns detected, pointing out that there is a need of improved imaging systems. Proliferation, neovascularization, lymphangiogenesis, invasion, circulation, and embolism are important steps in the pathogenesis of CM metastasis, with tumor vascularity as an important independent significant prognostic factor. The expression of chemokine receptors in cancer cells associated with the expression of the respective chemokine receptor ligands in the target sites of the metastasis is an interesting observation which may stimulate the development of new therapeutic strategies.
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PMID:The natural course of cutaneous melanoma. 1522 23


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