Clonal relationships between epidermotropic metastatic melanomas and their primary lesions: a loss of heterozygosity and X-chromosome inactivation-based analysis.
Loss of heterozygosity (LOH) has previously been demonstrated at multiple chromosome microsatellites in primary and metastatic melanomas. Epidermotropic metastases of melanoma are unique in their varied histopathologic appearance, which can mimic a primary lesion. Our objective was to compare LOH profiles in primary and epidermotropic metastatic melanoma to delineate their clonal relationship. We examined the pattern of allelic loss in the primary melanomas of nine patients in addition to the 21 corresponding epidermotropic metastatic melanomas (average 2.3 metastases per patient). DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser capture microdissection. Eight DNA microsatellite markers on six different chromosomes were analyzed: D1S214 (1p), D6S305 (6q), D9S171 (9p), D9S157 (9p), IFNA (9p), D10S212 (10q), D11S258 (11q), D18S70 (18q). In addition, X-chromosome inactivation analysis was performed in tumors from four women. LOH was seen in 67% (6/9) of primary melanomas and 81% (17/21) of epidermotropic metastatic melanomas. The most frequent allelic losses in informative cases occurred at 10q (33%), 9p (22%), and 11q (22%) in primary melanomas, and at 10q (50%), 1p (44%), and 6q (39%) in epidermotropic metastatic melanomas. Primary lesions demonstrating LOH had concordant allelic loss in at least one locus in a corresponding epidermotropic metastatic melanoma in 83% (5/6) of cases. X-chromosome analysis showed nonrandom inactivation in 75% (3/4) and 71% (5/7) of primary melanoma and epidermotropic metastatic melanoma cases, respectively. Our LOH and X-chromosome inactivation analysis data suggest that epidermotropically metastatic melanomas are clonally related to their primary lesion in many cases. Our data also indicated that some cases diagnosed as epidermotropic metastatic melanoma might be divergent clones or new primaries rather than metastatic disease.
Bahrami
Soon
S
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Cheng
Liang
L
Wang
Mingsheng
M
Jones
Timothy D
TD
Malone
Janine C
JC
Billings
Steven D
SD
D000328:Adult; D000369:Aged, 80 and over; D002878:Chromosomes, Human, Pair 1; D002879:Chromosomes, Human, Pair 10; D002880:Chromosomes, Human, Pair 11; D002887:Chromosomes, Human, Pair 18; D002896:Chromosomes, Human, Pair 6; D002899:Chromosomes, Human, Pair 9; D002999:Clone Cells / Q000473:pathology; D004817:Epidermis / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D018895:Microsatellite Repeats; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics; D016609:Neoplasms, Second Primary / Q000235:genetics* / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D049951:X Chromosome Inactivation