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)

The presence of regional lymph node metastases is one of the most significant prognostic factors for predicting survival in patients with clinical stage I or II cutaneous melanoma. For accurate staging of the primary tumor a sensitive technique is required to detect occult nodal micrometastases. This prospective diagnostic study was designed to evaluate the incidence of nodal micrometastases using nested reverse transcription-polymerase chain reaction (RT-PCR) for tyrosinase in comparison to immunohistochemical examination. Furthermore, the incidence of melanoma micrometastases detected by RT-PCR was analysed in correlation to major prognostic factors. A total of 466 regional lymph nodes from 79 patients with primary cutaneous melanoma (tumor thickness > 0.75 mm) were investigated. In 49 lymph nodes from 31 patients immunohistochemistry demonstrated melanoma metastases. Using tyrosinase RT-PCR, nodal micrometastases were detected in 136 lymph nodes from 52 patients including all lymph nodes positive by immunohistochemical examination. Out of the 417 lymph nodes negative by immunohistochemistry, 87 nodes (21%) were identified to express tyrosinase by the RT-PCR technique. Among the 48 patients negative by immunohistochemical assessment, 21 (44%) had nodal micrometastases (n = 40) using RT-PCR. All 68 lymph nodes from 46 non-melanoma patients serving as negative controls for tyrosinase RT-PCR were negative. The detection of melanocytic nodal micrometastases by tyrosinase RT-PCR is a highly specific method with a sensitivity significantly higher than that achieved by immunohistochemistry (p < 0.0001). Patients with nodal micrometastases identified exclusively by RT-PCR had significantly higher tumor thickness as compared to patients with negative results by RT-PCR (p < 0.01).
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PMID:Lymph node micrometastases of cutaneous melanoma: increased sensitivity of molecular diagnosis in comparison to immunohistochemistry. 969 21

To examine for the genetic basis of metastatic progression in cutaneous melanoma, we have compared loss of heterozygosity (LOH) of several selected chromosome regions that are implicated in the initiation and progression of melanoma, and alterations of the p16INK4a gene in 14 pairs of primary tumor and synchronous or asynchronous metastasis excised from the same patients. The most frequent genetic alteration during metastatic progression detected was the loss of p16INK4a protein expression (four of 14 cases), whereas no somatic p16INK4a gene mutations were found in any primary or metastatic tumors. LOH analyses showed that most of the chromosome losses including 6q, 8p, 9p, 9q, and 18q were shared between primary tumors and their metastases. Nevertheless, LOH of 6q and 11q and LOH of 7q not detected in primary tumors were, respectively, observed in two lymph node metastases. These results suggest that loss of p16INK4a protein expression (but not p16INK4a gene mutation) and the losses of chromosome arms 6q, 7q, and 11q play an important role in the acquisition of metastatic potential in sporadic melanoma. Furthermore, comparison of genetic profiles between the primary tumor and its metastasis revealed in several cases that heterogenous tumor cell populations might already exist at the early stage of tumorigenesis and evolve independently in the primary tumor and its metastasis, strongly suggesting that metastatic progression of sporadic melanoma is not accounted for by a linear progression model.
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PMID:Comparison of genetic profiles between primary melanomas and their metastases reveals genetic alterations and clonal evolution during progression. 985 96

Cutaneous metastases from melanoma can mimic primary melanoma and melanocytic nevi. Recognition of a metastatic lesion is of great importance for proper staging and treatment decisions. In this study, a potential diagnostic pitfall is described and discussed: dermal metastases from cutaneous melanoma simulating blue nevus, a phenomenon that has received little attention. Ten blue nevus-like lesions from three patients are presented. All contained pigmented melanocytes and melanophages in variable proportions arranged in a blue nevus-like growth pattern. The blue nevus-like metastases occurred in the same anatomic region as the primary tumor or, as in one patient, near the skin scar of a dissected lymph node metastasis. Histologic clues of metastatic melanoma included the presence of atypical epithelioid melanocytes, mitotic figures, and an associated inflammatory cell infiltrate at the periphery of the lesion. Although such histologic features facilitate the recognition of a metastasis, clinical correlation is essential for a definitive diagnosis.
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PMID:Metastatic melanoma to the skin simulating blue nevus. 1007 17

Progression and metastatic spread of primary cutaneous melanoma (PCM) is largely predicted by the thickness of the primary tumor. However, the accretive or proliferative pattern of growth of PCM is another aspect that might affect the prognosis. We retrieved from our histopathological files 11 superficial spreading PCM which had been documented to show an almost stable size for at least 3 years before excision. The area of the PCM at the skin surface had been measured by planimetry on the excision specimens. Histological sections were used to measure the maximum thickness of the neoplasms. A PCM volume estimate was derived by multiplying the surface area by the thickness of the tumors. In addition, the vessel area was determined beneath and outside the PCM lateral margins on Ulex europaeus agglutinin-1-stained sections using computer-assisted image analysis. Peritumoral vascularity was significantly more developed than at distance of the neoplasms. A significant negative exponential correlation was yielded between the peritumoral vascularity and the PCM volume estimate. Such vascular eclipse might be the cause of clinical PCM dormancy. However, other possible independent mechanisms are not ruled out by the present study.
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PMID:Vascular retardation in dormant growth-stunted malignant melanomas. 1049 82

There are fundamental issues regarding the role of integrins in human disease which remain to be elucidated. Human cutaneous melanoma is an attractive model for studying integrin involvement in tumor progression because it generally follows a sequential series of definable stages. Furthermore, the most specific marker for the transition of cells from the more benign, non-metastatic radial growth phase stage to the more malignant, metastatically competent vertical growth phase stage is associated with the onset of alpha v beta 3 integrin expression and function. This same pattern, however, does not hold true for human ocular/uveal melanomas which do not progress through these stages, but preferentially metastasize to the liver by dissemination of the cells via a direct hematogenous pathway. It is also unclear whether the alpha v beta 3 integrin is functionally involved in uveal melanoma metastasis or not. Our results show that perturbation of the alpha v beta 3 integrin on moderately invasive A375M human cutaneous melanoma cells with either specific antibodies or ligands results in an increase in the cells' ability to invade in vitro coincident with an increase in the cells' expression and extracellular levels of matrix metalloproteinase-2 (MMP-2, gelatinase A). The highly invasive C8161 human cutaneous melanoma cells express little-to-no alpha v beta 3 integrin, but are more invasive and express higher levels of MMPs after perturbation of their alpha 5 beta 1 integrin. This augmented invasiveness could subsequently be abrogated with a function-blocking anti-MMP-2 antibody. Primary uveal melanoma cells and cells derived from uveal metastases appear to grow in either a spindle or epithelioid morphology. The less invasive uveal melanoma cells are spindle shaped and express higher levels of the alpha v beta 3 integrin, while the more invasive cell lines are epithelioid shaped and express reduced levels of the alpha v beta 3 integrin. The apparent conflict between these results and the current model for cutaneous melanoma progression may be addressed as follows: The expression and function of the alpha v beta 3 integrin plays an important role(s) during the transition of cells from the radial growth phase stage to the vertical growth phase stage. However, further progression leading to metastases may require changes in the cells' integrins that would facilitate their ability to leave the primary tumor, and aid in their ability to invade and ultimately form metastases. It is also conceivable that the alpha v beta 3 integrin is reexpressed during various stages of metastatic dissemination, and, in particular, during tumor reestablishment.
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PMID:Molecular role(s) for integrins in human melanoma invasion. 1072 90

Histopathologic parameters of the primary tumor, such as Breslow's tumor thickness and Clark's level of invasion are the current basis for prognostic classifications of primary cutaneous melanoma. Once patients develop regional node metastasis, histopathologic features of the primary melanoma no longer contribute significantly to survival prediction. In this tumor stage, the extent of lymph node involvement is the main prognostic factor. This study addresses the question whether application of a highly sensitive molecular biology assay for detection of submicroscopic melanoma cells in sentinel lymph nodes may be suitable to improve melanoma staging. One hundred and sixteen patients with primary cutaneous melanoma with a total of 214 sentinel lymph nodes were enrolled. Sentinel lymph nodes were analyzed by histopathology including immunohistochemistry and by reverse transcription-polymerase chain reaction for tyrosinase. Patients were examined for tumor recurrences during a follow-up period of 19 mo (median). Disease-free survival probabilities were calculated and independent prognostic factors were determined by multivariate analysis. Using histopathology, micrometastatic nodal involvement was detected in 15 patients (13%). Of the 101 patients with histopathologically negative sentinel lymph nodes, 36 were reclassified by positive tyrosinase reverse transcription-polymerase chain reaction and 65 patients were still negative by reverse transcription-polymerase chain reaction. Recurrences were observed in 23 (20%) of 116 patients. These tumor recurrences were demonstrated in 10 patients (67%) with histopathologically positive sentinel lymph nodes, in nine patients (25%) with submicroscopic tumor cells detected by reverse transcription-polymerase chain reaction, and in four patients (6%) negative by both methods. The differences in recurrence rates were statistically significant (p = 0.01). In a multivariate analysis, histopathologic and reverse transcription-polymerase chain reaction status of the sentinel lymph node were demonstrated to be the only significant prognostic factors for predicting disease-free survival. Tyrosinase reverse transcription-polymerase chain reaction for the detection of minimal residual melanoma in sentinel lymph nodes is a powerful tool to determine patients who are at increased risk for subsequent metastasis. Moreover, a group of patients with high tumor thickness was identified by negative reverse transcription-polymerase chain reaction to be at low risk for recurrent disease. These data may have an impact on future tumor classifications of primary cutaneous melanoma.
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PMID:Examination of regional lymph nodes by sentinel node biopsy and molecular analysis provides new staging facilities in primary cutaneous melanoma. 1073 66

Considerable controversy surrounds the application of regional lymphadenectomy in the treatment of cutaneous melanoma in patients with clinically negative nodes; however, therapeutic lymph node dissection for clinically positive nodes has shown clear benefits. Opponents of elective lymph node dissection (ELND) for clinically negative nodes believe that because 80% of patients with clinical Stage I disease have histologically negative nodes at the time of resection of the primary tumor, prophylactic excision of the regional nodes is unnecessary. Some clinicians have failed to demonstrate a survival advantage for ELND. With the recent introduction of sentinel lymph node dissection, it may be possible to select patients who are likely to benefit from ELND. The authors recommend ELND based on the identification of metastatic cells within the sentinel lymph node in all patients with primary melanomas with a thickness of at least 1.0 mm.
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PMID:Regional lymph node dissections in malignant melanoma. 1094 63

The rapid incidence rise of cutaneous melanoma resulted in an increasing interest in this particular tumor. During the last years public prevention campaigns enlarged the awareness of melanoma, subsequently as a direct effect the mean tumor thickness of melanoma, the most predictable prognostic factor, decreased. Moreover, the biology of melanoma initiation and metastasis has been studied extensively with special interest in molecular biology. Controlled clinical studies answered several critical questions in respect to the standard care of surgery in melanoma. Yet, the guidelines for the surgical treatment of head and neck melanoma are in accordance to that of other localisations with reduced safety margins around the primary tumor. Elective (prophylactic) lymph node dissection (ELND) of regional lymph nodes is no more considered as a standard tool. Moreover, ELND has been given up by most melanoma centers, since it is known that prospective-randomized trials were not able to demonstrate an increase of overall survival for patients with ELND compared with untreated patients. Instead of this potentially aggressive treatment modality the examination of the first draining regional lymph node, sentinel node biopsy (SNB), has been introduced some years ago. Recently, a large clinical trial demonstrated that the SNB status reflects the most valuable prognostic factor for primary melanoma known so far. First studies in head and neck melanoma figured out that this technique is more complex in this special localisation, but produced comparable results. Systemic adjuvant (prophylactic) therapy of high-risk melanoma should preferentially be applied within controlled clinical trials. Most attractive candidates for an effective treatment are interferons. Several studies ruled out that interferon alpha-treated melanoma patients demonstrate an extended disease-free survival. Adjuvant chemotherapy has not shown a clinically relevant benefit. Thus, patients should preferentially be treated within controlled clinical trials.
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PMID:[Surgical and adjuvant drug therapy in head and neck cutaneous melanoma]. 1100 97

Management of cutaneous melanoma becomes more difficult as tumor cells metastasize to sites that are remote from the primary tumor. There is a hierarchy of risk associated with cancer spread by different routes and to different organs. Differences in clinical outcome indicate critical variations in pathobiology at different stages in disease evolution. Prevention of the evolution of melanoma is critical, especially beyond the stage of nodal involvement.
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PMID:The shifting patterns of metastatic melanoma. 1122 14

The American Joint Committee on Cancer (AJCC) staging system for melanoma has recently been revised and published. The previous staging system had not been substantially modified since the late 1980s. In a series of papers, the staging system for melanoma was critically analyzed, and many shortcomings were identified. Many well-established prognostic factors were not used in the staging system. This assessment has led to a substantially modified staging system for cutaneous melanoma in 2001 that is a considerable improvement over past staging systems, albeit more complex. The following modifications are the most important: 1) The primary determinant of tumor (T) staging is tumor thickness as measured in millimeters. The Clark level of invasion is now used only for defining T1 (< or = 1mm) melanomas; 2) The cutpoints for tumor thickness are less than or equal to 1 mm, 1 to 2 mm, 2 to 4 mm, and greater than 4 mm; 3) Ulceration has been added in describing the primary tumor; 4) Local recurrence, satellite disease, and in-transit metastases have similar prognosis and are now all classified together as regional stage III disease; 5) Size of lymph node as prognostic factor has been eliminated and replaced with the number of positive nodes; 6) The presence of an elevated serum lactic dehyrogenase level is used in the metastasis (M) category. This revised staging system more precisely defines prognosis and will improve the stratification of patients in future clinical trials.
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PMID:Review of the 2001 AJCC staging system for cutaneous malignant melanoma. 1138 18


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