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)

Adequate wide excision of a primary cutaneous melanoma is associated with a 10-year cure rate of 85% when the tumor's depth is less than 1.5 mm (American Joint Committee on Cancer [AJCC] Stage I). However, 50% of patients with deep (> 4 mm) primary melanomas, 60-85% of those with regional lymph node metastases (AJCC Stage III), and 95% of those with metastases to distant sites (AJCC Stage IV) will experience recurrence, which is associated with a dismal prognosis. Adjuvant therapy of melanoma assumes that treatment will be more effective when the tumor burden is small. In the 1970s and 1980s, randomized trials tested the efficacy of chemotherapy, nonspecific immunotherapy, levamisole, and regional perfusion therapy in patients with AJCC Stage II and III melanoma. Dacarbazine (DTIC) alone or in combination with other chemotherapeutic drugs or with nonspecific immunotherapy did not significantly improve disease free or overall survival. Of the four levamisole trials, only the study conducted by the National Cancer Institute of Canada revealed a reduction in recurrence and mortality; however, this reduction was not significant by multivariate analysis. The value of regional perfusion therapy following resection of high risk extremity melanomas is currently being determined by multiinstitutional studies conducted by the World Health Organization and the North American Perfusion Group. Multi-institutional trials also are examining the adjuvant role of interferon-alpha in patients with deep (> 3 mm) primary melanomas or positive regional lymph nodes; results should reveal its optimum dose and duration of treatment (3 x 10(6) U for > or = 2 years versus 10 x 10(6) U/m2 for 1 year, subcutaneously 3 times a week) and its impact on survival. A randomized trial of interferon-gamma undertaken by the Southwest Oncology Group was discontinued after interim analysis indicated an adverse effect. Phase II trials indicate that active specific immunotherapy can alter the natural course of AJCC Stage III and IV melanoma following surgical resection of nodal or distant metastases. Upcoming results of Phase III trials will establish the role of active specific immunotherapy for adjuvant treatment of patients with resected AJCC Stage III and IV melanoma.
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PMID:The role of adjuvant therapy in melanoma management. 780 1

The BCL-2 gene is the prototype of a newly described family of oncogenes involved in tumorigenesis by blocking apoptosis, or programmed cell death. Overexpression of BCL-2 protein was originally described in follicular B-cell lymphomas bearing the 14;18 translocation. BCL-2 overexpression has also been described in other lymphomas and more rarely in neoplasms outside the lymphoid tissue. The aim of this paper is to determine the immunohistochemical expression of BCL-2 in intradermal nevi and primary invasive and metastatic melanoma. Formalin-fixed and paraffin-embedded tissues from 4 cutaneous melanoma metastases, 10 primary invasive melanomas, and 10 intradermal melanocytic nevi were immunolabeled with monoclonal antibodies directed against BCL-2 protein (Dako, clone 124) and Ki-67 antigen (Amac, clone MIB-1), after antigen retrieval techniques. Morphologically normal epidermal melanocytes expressed BCL-2, as did nevi and melanomas in virtually all cells. However, whereas the labeling in normal melanocytes and nevus cells showed a uniformly strong reactivity, melanoma cells showed a variable but mainly weak reactivity. Ki-67 antigen expression was restricted to melanomas. The widespread expression of BCL-2 suggests that this oncoprotein cannot be involved in the malignant transformation of melanocytic cells. It seems likely that the decreased BCL-2 expression detected in melanomas may reflect one further step of tumor progression in melanocytic neoplasms.
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PMID:Immunohistochemical expression of BCL-2 in melanomas and intradermal nevi. 786 49

Mutations in N-ras exon 2 codon 61 were studied in formalin-fixed human melanoma metastases. DNA fragments including codon 61 were amplified by polymerase chain reaction (PCR) and mutational analysis was performed by oligonucleotide hybridization (ODN), allele specific PCR and PCR combined with single strand conformation polymorphism analysis (SSCP). Thirty metastases from 25 patients with 'spontaneous' cutaneous melanoma were compared with 35 metastases from 17 patients with 'hereditary' cutaneous melanoma. The frequency of mutations as measured by PCR/ODN was significantly higher in patients with hereditary melanoma (mutations in 24% versus 59%, p < 0.05). The most frequent mutations were C/A transversions to lysine (AAA). The occurrence of lysine mutations was, in addition, studied by allele specific polymerase chain reaction. Again, the mutation frequency was significantly higher in metastases from patients with hereditary melanoma. PCR/SSCP finally enabled the isolation of lysine mutant alleles and nucleotide sequence analysis which confirmed the presence of the mutated codon 61. The relatively higher frequency of N-ras mutations in tumours from patients with hereditary melanoma may be related to the hypermutability described in hereditary melanoma and dysplastic naevus syndrome. The results support an involvement of N-ras mutations in the molecular pathogenesis of melanoma.
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PMID:Melanoma metastases from patients with hereditary cutaneous malignant melanoma contain a high frequency of N-ras activating mutations. 791 62

A positive correlation between PCNA and the most important histoprognostic factors of cutaneous melanoma has been demonstrated. The aim of our work was to evaluate the efficacy of PCNA in predicting melanoma recurrence and to compare it with that of Breslow thickness. One-hundred and fifteen patients (75 women, 40 men; mean age 50 years) with primary cutaneous melanoma were retrieved. pTNM stages were as follows: stage I, 54 patients; stage II, 31 patients; stage III, 26 patients; and stage IV, four patients. The mean follow-up period was 55 months (range 2-260). Six patients developed lymph node metastases and 28 developed distant metastases; 27 patients died within 2-202 months from diagnosis. Tumour thickness was re-evaluated for each case. PCNA immunostaining was performed using the avidin-biotin complex method and the percentage of PCNA-positive tumour cells was indicated as the PCNA index. In order to evaluate and compare the PCNA index and Breslow thickness as predictors of recurrence, the receiver-operating characteristic (ROC) curve method, based on true-positive and false-positive rates was used. The PCNA index showed the highest true-positive rates and the lowest false-positive rates in the 5-30 interval. The PCNA index optimal cut-off is 20, characterized by 70% sensitivity and 80% specificity; Breslow thickness optimal cut-off is 3.5 mm, with 40% sensitivity and 90% specificity. Our results indicate that the PCNA index has a higher efficacy in predicting locoregional and distant recurrences in patients presenting primary cutaneous melanoma.
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PMID:Proliferating cell nuclear antigen (PCNA) and recurrence in patients with cutaneous melanoma. 795 Mar 56

A total of 107 patients with cutaneous melanoma had parotidectomies performed by one surgeon over a 6-year period. Twenty-five parotidectomies were therapeutic and 82 were elective. All elective and 18 therapeutic operations entailed superficial lobectomy, and there were 4 total and 3 subtotal therapeutic operations. The facial nerve was completely preserved in 97 operations, partially sacrificed in 8, and totally sacrificed in 2. Neck dissection accompanied all but 1 parotidectomy. The most common postoperative complication was facial nerve dysfunction. A total of 33 of 82 patients had lower lip weakness between 6 months and 5 years after elective parotidectomy. Lymph nodes were pathologically positive in the parotid gland in 27 patients and in the neck in 15 patients. Ten patients had both parotid and neck metastases. Among patients with positive melanoma in the parotid gland who were observed for at least 1 year, 16 received adjuvant postoperative radiotherapy (550 cGy x 5 fractions) and 9 did not. Parotid recurrences developed in 1/16 irradiated and 4/9 nonirradiated patients but this difference was not significant. Overall melanoma-specific survival at 5 years was 64%, with nodal involvement in the neck or parotid gland significantly worsening prognosis (40% survival at 5 years). The roles of elective lymphadenectomy and adjuvant radiotherapy are now being examined in prospective randomized clinical trials.
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PMID:Evaluation of 107 therapeutic and elective parotidectomies for cutaneous melanoma. 797 59

The authors report the casual discovery in 1991 of a metastasis during Tc-99m MDP imaging of a 57-year-old woman who underwent surgery in 1983 for cutaneous melanoma on the right calf. The scan did not show bone alterations but did reveal an area of hyperactive uptake in the soft tissue of the medial surface of the thigh, where slightly altered pigmentation was also apparent. A subsequent immunoscan with Tc-99m-F(ab')2 225.28S confirmed increased uptake at this site. The lesion was removed and was histologically diagnosed as a skin metastasis from melanoma. Inguinal adenopathy appeared 6 months later. The uptake of Tc-99m MDP by both primary and metastases tumors has been described, although this may be the first report concerning melanoma. The uptake mechanism is not known.
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PMID:Casual discovery of Tc-99m MDP uptake for melanoma metastasis in soft tissue. 798 9

A phase lb trial of a novel regional approach to adoptive immunotherapy is reported. Patients with liver metastases received continuous high-dose infusion of interleukin-2 (IL-2) into the splenic artery or intravenous infusion with subsequent transfer of lymphokine-activated killer (LAK) cells into the portal vein or the hepatic artery. Trafficking studies revealed homogeneous distribution of the LAK cells within the liver. The usual side-effects of IL-2 and LAK cells occurred without limiting liver toxicity. One partial (7+ months) and two complete responses (36 and 26+ months) were observed in 9 patients with metastases from cutaneous melanoma. None of 6 patients with metastases from ocular melanoma responded.
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PMID:Regional adoptive immunotherapy with interleukin-2 and lymphokine-activated killer (LAK) cells for liver metastases. 814 49

The prognostic significance of the BANS region (Back, Arms, Neck, Scalp) in primary cutaneous melanoma remains controversial. We hypothesized that the different anatomic sites of the BANS region may have different prognostic significance. As the anatomic areas examined have varied between reports on BANS or head and neck melanomas, these differences could explain the lack of consistent findings. Between 1971-1990 more than 5000 patients with Stage I (n = 2576) and Stage II (n = 852) cutaneous melanoma were treated at the UCLA Medical Center. Patients were stratified for analysis into the following anatomic categories: scalp, neck, upper back, arm, and other anatomic sites. Initial analysis revealed that Clark's level of invasion, tumor thickness, gender, and number of positive nodes were predictive of survival. Controlling for these variables, the impact of the site of origin on prognosis was evaluated. Five-year actuarial survival in Stage I patients was as follows: scalp--80 per cent, neck--92 per cent, upper back--90 per cent, arm--94 per cent, all others--89 per cent. There were no significant survival differences between these groups, although the poorer survival for scalp primaries approached statistical significance (P = 0.084). In Stage II disease, however, marked survival differences were noted between anatomic sites. median survival for Stage II patients was as follows: scalp--25 months, neck--28 months, upper back--38 months, arm--75 months, all others--67 months (P = 0.005). These results indicate that anatomic site of origin does affect prognosis in patients with nodal metastases.
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PMID:Evaluation of the prognostic significance of the site of origin of cutaneous melanoma. 816 Oct 88

In the attempt to contribute to a correct and early diagnosis of melanoma, this paper critically evaluates, in 40 patients with cutaneous localization and 20 with ocular localization, the results of immunoscintigraphy with 99mTc-225.28S-F(ab')2 and the clinical, instrumental and biopsy findings. While the cutaneous melanoma group is mainly composed of patients subjected to surgical exeresis of the lesion before radioimmunoscintigraphy (RIS), the ocular melanoma group is composed of patients with the primary lesion in situ or previously treated with contact radiotherapy. In the cutaneous melanoma group 5 cases presented falsely positive immunoscintigraphic findings, and only 2 falsely negative. In the ocular melanomas, the percentage of false negatives was higher (n = 7). This is probably attributable to the antigenic expressivity, higher in the metastases than in the primary melanomas. The cases of particular interest are discussed in relation to the clinical picture, to the instrumental examinations and to the histological findings. The work made it possible to contribute to a more correct interpretation of the RIS findings in the staging and follow-up of cutaneous and ocular melanomas.
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PMID:Radioimmunoscintigraphy with 99mTc-225.28S-F(ab')2 in cutaneous and ocular melanomas: cases of particular clinical interest. 817 59

We performed a prospective study of the results of treatment of primary cutaneous melanoma of the foot in 282 patients to determine if there were any factors that could predict survival. These patients were part of a group of 1018 patients who had primary cutaneous melanoma affecting the lower extremity. We found that 184 (65 per cent) of the 282 patients had a tumor that extended into the reticular dermis or subcutaneous tissue (a Level-IV or V lesion according to the system of Clark et al.). Sixty-three patients (22 per cent) had evidence of local, regional, or distant metastatic disease at the time of presentation. Location of the melanoma on the plantar aspect of the foot was found to be an independent variable that was associated with a poorer rate of survival (56 per cent at five years and 46 per cent at ten years) compared with a dorsally located melanoma (80 per cent at five years and 67 per cent at ten years). Subungual lesions were associated with an extremely low rate of survival (17 per cent at ten years); however, because of the small number of subungual lesions that were followed, the difference in survival between the patients who had a plantar lesion and those who had a subungual lesion was not significant (p = 0.52). Variables, in order of decreasing importance, that had independent prognostic significance for survival of patients who had a melanoma of the foot were the clinical stage of the lesion at the time of presentation (p < 0.001) and the age of the patient (p < 0.03), as determined by multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Melanoma of the foot. 820 Aug 96


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