Fluorescence in situ hybridization (FISH) as an ancillary diagnostic tool in the diagnosis of melanoma.
Although the clinical and pathologic diagnosis of some melanomas is clear-cut, there are many histopathologic simulators of melanoma that pose problems. Over-diagnosis of melanoma can lead to inappropriate therapy and psychologic burdens, whereas under-diagnosis can lead to inadequate treatment of a deadly cancer. We used existing data on DNA copy number alterations in melanoma to assemble panels of fluorescence in situ hybridization (FISH) probes suitable for the analysis of paraffin-embedded tissue. Using FISH data from a training set of 301 tumors, we established a discriminatory algorithm and validated it on an independent set of 169 unequivocal nevi and melanomas as well as 27 cases with ambiguous pathology, for which we had long-term follow-up data. An algorithm-using signal counts from a combination of 4 probes targeting chromosome 6p25, 6 centromere, 6q23, and 11q13 provided the highest diagnostic discrimination. This algorithm correctly classified melanoma with 86.7% sensitivity and 95.4% specificity in the validation cohort. The test also correctly identified as melanoma all 6 of 6 cases with ambiguous pathology that later metastasized. There was a significant difference in the metastasis free survival between test-positive and negative cases with ambiguous pathology (P=0.003). Sufficient chromosomal alterations are present in melanoma that a limited panel of FISH probes can distinguish most melanomas from most nevi, providing useful diagnostic information in cases that cannot be classified reliably by current methods. As a diagnostic aid to traditional histologic evaluation, this assay can have significant clinical impact and improve classification of melanocytic neoplasms with conflicting morphologic criteria.
Gerami
Pedram
P
Department of Dermatology and the Lurie Cancer Center, Northwestern University, The Feinberg School of Medicine University of California, San Francisco, CA, USA.
Jewell
Susan S
SS
Morrison
Larry E
LE
Blondin
Beth
B
Schulz
John
J
Ruffalo
Teresa
T
Matushek
Paul
P
Legator
Mona
M
Jacobson
Kristine
K
Dalton
Scott R
SR
Charzan
Susan
S
Kolaitis
Nicholas A
NA
Guitart
Joan
J
Lertsbarapa
Terakeith
T
Boone
Susan
S
LeBoit
Philip E
PE
Bastian
Boris C
BC
D000293:Adolescent; D000328:Adult; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000235:genetics*; D002648:Child; D005260:Female; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008545:Melanoma / Q000145:classification / Q000175:diagnosis* / Q000235:genetics*; D018332:Nevus, Epithelioid and Spindle Cell / Q000175:diagnosis / Q000235:genetics; D012372:ROC Curve; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics
D014408:Biomarkers, Tumor