Prognostic significance of allelic losses in primary melanoma.
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 significantly 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 significantly correlated with disease-free survival (P=0.013), with an increase in FAL associated with a poorer outcome; this association remained significant when controlled for tumour thickness (P=0.035). In addition, a greater proportion of cells were immunopositive for Ki67 antigen, p53 and p21WAF1 protein in the primary melanomas than in the benign melanocytic nevi, however, only p53 over-expression was significantly associated with improved survival (P=0.041).
Healy
E
E
Department of Dermatology, University of Newcastle upon Tyne, UK.
Belgaid
C
C
Takata
M
M
Harrison
D
D
Zhu
N W
NW
Burd
D A
DA
Rigby
H S
HS
Matthews
J N
JN
Rees
J L
JL
D000483:Alleles; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002872:Chromosome Deletion; D002879:Chromosomes, Human, Pair 10; D002896:Chromosomes, Human, Pair 6; D002899:Chromosomes, Human, Pair 9; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D018572:Disease-Free Survival; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D019656:Loss of Heterozygosity; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53