Diagnosis of cutaneous melanocytic tumours by four-colour fluorescence in situ hybridisation.
BACKGROUND
Accurate classification of primary melanocytic tumours as benign or malignant is crucial for prognostic prediction and appropriate patient management. Several chromosomal aberrations have been frequently identified in melanomas, but are absent in melanocytic naevi. We performed four-colour fluorescence in situ hybridisation (FISH) analysis of melanocytic tumours to determine the accuracy of the technique in classifying melanocytic tumours as benign or malignant.


METHODS
FISH was performed on paraffin-embedded tissue from 40 histologically unequivocal melanocytic tumours (10 metastatic melanomas, 10 primary melanomas and 20 benign melanocytic naevi) using the product Vysis LSI RREB1/LSI MYB/LSI CCND1/CEP 6 probes (Abbott Molecular Laboratories, USA), which is designed to detect the copy number of the RREB1 (6p25), MYB (6q23), and CCND1 (11q13) genes and FISH positivity is defined by means of a scoring algorithm.


RESULTS
FISH distinguished the melanomas and the naevi with a sensitivity of 90% (10/10 primary melanoma cases and 8/10 metastatic melanoma cases, respectively), and a specificity of 95%. The most common abnormalities in the melanomas were increased copies of 11q (70%) and 6p (70%), followed by 6q loss relative to cep6 (50%). Fifteen of the 18 positive melanomas were positive by more than one criterion.


CONCLUSIONS
The results of this study show that FISH, using a panel of four probes, is a sensitive and specific method of classifying benign and malignant melanocytic tumours. The four-colour FISH technique has the potential to assist in the stratification of the subgroup of melanocytic tumours which are difficult to classify using conventional histology.
Morey
Adrienne L
AL
Department of Anatomical Pathology, St Vincent's Hospital, Darlinghurst, NSW, Australia.
Murali
Rajmohan
R
McCarthy
Stanley W
SW
Mann
Graham J
GJ
Scolyer
Richard A
RA
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D019938:Cyclin D1 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D020570:Genes, myb; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000235:genetics*; D008875:Middle Aged; D009508:Nevus, Pigmented / Q000175:diagnosis / Q000235:genetics; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D055815:Young Adult
D004268:DNA-Binding Proteins; C101743:RREB1 protein, human; D014157:Transcription Factors; D019938:Cyclin D1