Relation of Cytogenetic Abnormalities and Clinical Outcome in Metastatic Melanoma

Trent, Jeffrey M.; Meyskens, Frank L.; Salmon, Sydney E.; Ryschon, Kay; Leong, Stanley P. L.; Davis, John R.; McGee, Daniel

doi:10.1056/nejm199005243222107

Cited by 91 publications

(43 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several other preclinical parameters have been reported to correlate with disease progression in melanoma, including cytogenetic abnormalities, DNA ploidy and S-phase fraction, the expression of metastasis associated gene products, elevated serum levels of soluble adhesion molecules and the detection of circulating melanoma cells in peripheral blood using reverse transcription-polymerase chain reaction (RT-PCR) for tyrosinase messenger RNA (Trent et al, 1990;Smith et al, 1991;Xerri et al, 1994;Karlsson et al, 1996;Kunter et al, 1996). These parameters could reflect increase in the total tumour mass, recurrence of the disease or the presence of occult melanoma.…”

Section: Resultsmentioning

confidence: 99%

Elevated serum levels of S100 and survival in metastatic malignant melanoma

Buer

Probst²,

Franzke³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

Summary Current reports suggest serum S100 as a prognostic marker for disease progression in advanced malignant melanoma. In this study, we assessed serum levels of S100 and multiple clinical factors in relation to overall survival in 99 patients with metastatic malignant melanoma seen at our institution between May 1990 and April 1996. For statistical analysis, we used both univariate and multivariate Cox proportional-hazards models. Elevated serum levels of S100 correlated with poor outcome in metastatic malignant melanoma (P < 0.0001), univariate analysis). Upon multivariate analysis, however, S100 added no information to known clinical prognostic parameters.

show abstract

Section: Resultsmentioning

confidence: 99%

Elevated serum levels of S100 and survival in metastatic malignant melanoma

Buer

Probst²,

Franzke³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…Investigations on cutaneous melanoma have demonstrated that multiple genetic abnormalities exist within these tumours (reviewed in Rees and Healy, 1996). Cytogenetic studies have detected gains and losses of genetic material on multiple chromosomes, and subsequent studies on loss of heterozygosity (LOH) have con®rmed the ®nding of frequent allelic loss (Cowan et al, 1988;Dracopoli et al, 1989;Trent et al, 1990;Millikin et al, 1991;Fountain et al, 1992;Isshiki et al, 1993Isshiki et al, , 1994Herbst et al, 1994;Holland et al, 1994;Walker et al, 1994;Healy et al, 1995Healy et al, , 1996aThompson et al, 1995). Recent work has shown that 6q, 9p and 10q are the chromosome arms most frequently lost in this tumour, with evidence that allelic losses on 6q and 10q may be responsible for the malignant phenotype in this neoplasm (Healy et al, 1996a).…”

Section: Introductionmentioning

confidence: 90%

“…Some (but not all) studies on DNA ploidy in melanoma have suggested that individuals with tumours exhibiting aneuploidy have a poorer outcome, but there is little information on which chromosomes are responsible for this (Muhonen et al, 1992;Heaton et al, 1993;Scheistroen et al, 1995;Umebayashi and Otsuka, 1995). Trent et al (1990) investigated metastatic melanomas for cytogenetic aberrations in relation to clinical outcome, and documented that individuals with structural abnormalities of chromosomes 7 and 11 had signi®cantly shorter survival than patients without these abnormalities. However, metastatic melanoma is a late stage of disease, and nearly all patients with metastases will eventually die from their melanoma (Barth et al, 1995;Lee et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of allelic losses in primary melanoma

et al. 1998

View full text Add to dashboard Cite

Loss of genetic material, including loss of loci on chromosome arms 6q, 9p, and 10q, occurs frequently in cutaneous melanoma but infrequently in benign melanocytic nevi or other melanocytic lesions, suggesting that these genetic alterations are important in the development and progression of melanoma. To examine whether allelic loss is of prognostic importance in melanoma, disease-free survival was related to loss of heterozygosity on 6q, 9p and 10q in 83 individuals with sporadic primary cutaneous melanoma. Loss of chromosome arms 6q and 10q were each signi®cantly associated with a poorer clinical outcome (P=0.013 and P=0.001 respectively). In a subgroup of 41 subjects whose primary tumours were allelotyped, the fractional allelic loss (FAL) at 39 autosomal arms also signi®cantly correlated with disease-free survival (P=0.013), with an increase in FAL associated with a poorer outcome; this association remained signi®cant when controlled for tumour thickness (P=0.035). In addition, a greater proportion of cells were immunopositive for Ki67 antigen, p53 and p21 WAF1 protein in the primary melanomas than in the benign melanocytic nevi, however, only p53 overexpression was signi®cantly associated with improved survival (P=0.041).

show abstract

“…The data obtained are quite complex and not always unambiguous. However, the non-random involvement of chromosomes 1, 6, 7 and 9 has been published repeatedly (Chen et al, 1973;Koprowski et al, 1985;Heim et al, 1988;Trent at al, 1990;Balch et al, 1992). Deletions or loss of function of the p53 tumour-suppressor gene (p53-TSG) have been found in roughly 50% of all malignant tumours .…”

Section: Malignant Melanoma (Mm) Is a Common Cancer Amongmentioning

confidence: 99%

Deletions of the region 17p11-13 in advanced melanoma revealed by cytogenetic analysis and fluorescence in situ hybridization

et al. 1998

View full text Add to dashboard Cite

Malignant melanoma (MM) is a common cancer amongCaucasians and has shown a deplorable increase in incidence rates during recent decades. Early diagnosis -and consequently early surgical excision -has been greatly improved, leading to an average 5-year survival rate of up to 80%. Therefore, stable incident death rates of MM could be observed. However, the prognosis of metastatic MM still remains poor, with a long-term survival rate of about 20% in stage III patients (Balch et al, 1992;Johnson et al, 1995).Cytogenetic analyses of cell lines derived from MM have been reported for more than 20 years (Chen et al, 1973). The data obtained are quite complex and not always unambiguous. However, the non-random involvement of chromosomes 1, 6, 7 and 9 has been published repeatedly (Chen et al, 1973;Koprowski et al, 1985;Heim et al, 1988;Trent at al, 1990;Balch et al, 1992). Deletions or loss of function of the p53 tumour-suppressor gene (p53-TSG) have been found in roughly 50% of all malignant tumours . Mutations of the p53-TSG have been found to be characteristic for carcinogenes and biochemical mechanisms responsible for genetic lesions in DNA that cause cancer (Harris et al, 1993). Loss of function of p53 has been reported for colon, oesophageal squamous cell, pancreatic and hepatic carcinoma and other malignant tumours of the brain, lung, breast and ovary (Levine, 1993). Despite numerous studies, no clear information on the role of p53 in MM is available to date (Stretch et al, 1991;Akslen et al, 1992;Catresana et al, 1993;Piepkorn, 1994;Kanoko et al, 1995;Poremba et al, 1995;Saez-Santamaría et al, 1995;Talve et al, 1996). The majority of cultured MM cell lines is described to express p53 protein as assessed by monoclonal antibody binding. Point mutations in the p53 coding sequence (usually cytosine to thymidine) have been found in 30% of cases (Piepkorn, 1994). Stretch et al report that 73% of primary and 93% of metastatic melanomas express mutant p53 protein (Stretch et al, 1991). However, there are also reports describing a reduced p53 expression in metastatic MM compared with primary lesions (Catresana et al, 1993).To investigate the role of p53-TSG in metastatic MM, we analysed 11 metastatic MM derived from 11 patients cytogenetically by chromosome banding techniques and FISH after shortterm culture. In addition, paraffin-embedded tissues of 9 of the 11 MM were examined immunohistochemically using DO-7, an antibody reacting with both wild-type and mutant p53 protein. MATERIAL AND METHODS MaterialEleven surgically removed, histologically confirmed metastatic MM (ME 1 to ME 11) from 11 patients were minced with scissors and prepared for short-term culture by standard methods (Pederson et al, 1986). Patients' data are briefly described in Table 1. For preparing MM specimens for cytogenetic investigation, collagenase (Worthington Biochemical Corporation, NJ, USA) 200 U ml -1 was used over night.The next day, cells were washed three times to start cultivation in a collagenase-free medium with RPMI-1640 medium (Sera-l...

show abstract

Relation of Cytogenetic Abnormalities and Clinical Outcome in Metastatic Melanoma

Cited by 91 publications

References 10 publications

Elevated serum levels of S100 and survival in metastatic malignant melanoma

Elevated serum levels of S100 and survival in metastatic malignant melanoma

Prognostic significance of allelic losses in primary melanoma

Deletions of the region 17p11-13 in advanced melanoma revealed by cytogenetic analysis and fluorescence in situ hybridization

Contact Info

Product

Resources

About