PMID- 19561450 OWN - NLM STAT- MEDLINE DCOM- 20090818 LR - 20220318 IS - 1532-0979 (Electronic) IS - 0147-5185 (Linking) VI - 33 IP - 8 DP - 2009 Aug TI - Fluorescence in situ hybridization (FISH) as an ancillary diagnostic tool in the diagnosis of melanoma. PG - 1146-56 LID - 10.1097/PAS.0b013e3181a1ef36 [doi] AB - 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. FAU - Gerami, Pedram AU - Gerami P AD - Department of Dermatology and the Lurie Cancer Center, Northwestern University, The Feinberg School of Medicine University of California, San Francisco, CA, USA. FAU - Jewell, Susan S AU - Jewell SS FAU - Morrison, Larry E AU - Morrison LE FAU - Blondin, Beth AU - Blondin B FAU - Schulz, John AU - Schulz J FAU - Ruffalo, Teresa AU - Ruffalo T FAU - Matushek, Paul 4th AU - Matushek P 4th FAU - Legator, Mona AU - Legator M FAU - Jacobson, Kristine AU - Jacobson K FAU - Dalton, Scott R AU - Dalton SR FAU - Charzan, Susan AU - Charzan S FAU - Kolaitis, Nicholas A AU - Kolaitis NA FAU - Guitart, Joan AU - Guitart J FAU - Lertsbarapa, Terakeith AU - Lertsbarapa T FAU - Boone, Susan AU - Boone S FAU - LeBoit, Philip E AU - LeBoit PE FAU - Bastian, Boris C AU - Bastian BC LA - eng GR - R01 CA131524/CA/NCI NIH HHS/United States PT - Journal Article PL - United States TA - Am J Surg Pathol JT - The American journal of surgical pathology JID - 7707904 RN - 0 (Biomarkers, Tumor) SB - IM EIN - Am J Surg Pathol. 2010 May;34(5):688 MH - Adolescent MH - Adult MH - Algorithms MH - Biomarkers, Tumor/*genetics MH - Child MH - Female MH - Gene Dosage MH - Humans MH - *In Situ Hybridization, Fluorescence MH - Melanoma/classification/*diagnosis/*genetics MH - Nevus, Epithelioid and Spindle Cell/diagnosis/genetics MH - ROC Curve MH - Sensitivity and Specificity MH - Skin Neoplasms/*classification/*diagnosis/genetics EDAT- 2009/06/30 09:00 MHDA- 2009/08/19 09:00 CRDT- 2009/06/30 09:00 PHST- 2009/06/30 09:00 [entrez] PHST- 2009/06/30 09:00 [pubmed] PHST- 2009/08/19 09:00 [medline] AID - 10.1097/PAS.0b013e3181a1ef36 [doi] PST - ppublish SO - Am J Surg Pathol. 2009 Aug;33(8):1146-56. doi: 10.1097/PAS.0b013e3181a1ef36.