Fluorescence In Situ Hybridization (FISH) as an Ancillary Diagnostic Tool in the Diagnosis of Melanoma

Gerami, Pedram; Jewell, Susan; Morrison, Larry E.; Blondin, Beth; Schulz, John; Ruffalo, Teresa; Matushek, Paul; Legator, Mona S.; Jacobson, Kristine; Dalton, Scott R.; Charzan, Susan; Kolaitis, N.A.; Guitart, Joan; Lertsbarapa, Terakeith; Boone, Susan L.; LeBoit, Philip E.; Bastian, Boris C.

doi:10.1097/pas.0b013e3181a1ef36

Cited by 432 publications

(457 citation statements)

References 33 publications

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“…10,12,13 However in Morey's study, CCDN1 gain was as frequent as RREB1 gain in all type of melanomas (70%), 12 whereas we observed only 48% of CCDN1 gain in FISH-positive cases. CCDN1 gain has been found associated with ALM and chronically sun-damaged skin melanoma subtypes.…”

Section: Discussioncontrasting

confidence: 75%

“…Concerning false-negative cases, our three FISH-negative melanomas were thin SSM (Breslow) between 1.2 and 2 mm. However, the impact of thickness on FISH results was not shown by the study by Gerami et al 10 A recent study proved the feasibility of this FISH test for in situ (very thin) melanocytic lesions in the so-called lentiginous junctional melanoma of the elderly. 14 In this study, three out of 19 in situ melanomas were FISH negative.…”

Section: Discussionmentioning

confidence: 96%

“…Thirty nuclei were analyzed under high power ( Â 100) objective. The criteria for FISH positivity were provided recently by Gerami et al: 10 (A) gain in RREB1 relative to CEP6 greater than 55%; (B) gain in RREB1 greater than 29%; (C) loss of MYB relative to CEP6 greater than 40% and (D) gain in CCDN1 greater than 38%. The cases were considered as polyploid when all signals were simultaneously greater than 2 in the majority of nuclei examined.…”

Section: Fish Analysismentioning

confidence: 99%

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Fluorescence in situ hybridization, a diagnostic aid in ambiguous melanocytic tumors: European study of 113 cases

et al. 2011

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Some melanocytic tumors are ambiguous, so the reproducible histopathological diagnosis of benign or malignant lesion is difficult. This study evaluated the contribution of fluorescence in situ hybridization (FISH) first in 43 non-equivocal melanomas and nevi, and then in 113 ambiguous melanocytic tumors selected by expert pathologists from six different European institutions. We included two groups of ambiguous tumors: patients without recurrence (5-year minimal follow-up) and with metastases. An independent triple-blind histopathological review was performed to classify tumors as 'favor benign' (AÀ) or 'favor malignant' (A þ ). A four-color probe set targeting 6p25, 6q23, 11q13 and CEP6 was used for FISH. In the 43 non-equivocal melanomas and nevi, sensitivity was 85% and specificity 90%. Ninety out of 95 ambiguous melanocytic tumors included were FISH interpretable (67 FISH negative and 23 FISH positive). Of the 90 patients, 69 presented no recurrence and 21/90 exhibited metastases. These ambiguous tumors were mostly spitzoid tumors (45/90). Histopathological reviewers classified these tumors as favor malignant (49/90) and favor benign (32/90), whereas nine cases had a discordant diagnosis. By comparison with outcome, the sensitivity and specificity of histopathological review were 95 and 52%, and the sensitivity and specificity of FISH were 43 and 80%. Compared with histopathological review, the sensitivity and specificity of FISH were 34.5 and 91%. Interestingly, by combining the histopathological diagnosis with FISH results, the diagnosis was optimized, especially by increasing specificity (76% instead of 52% for expert diagnosis alone) and by improving sensitivity compared with FISH alone (90 vs 43% for FISH result alone). The value of this FISH test is to add a reproducible demonstration of malignancy to the histopathological diagnosis, especially in doubtful/ambiguous melanocytic tumors. A positive FISH test reinforces the diagnosis of melanoma, allowing such tumors (particularly thick tumors) to be managed as melanomas.

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Section: Discussioncontrasting

confidence: 75%

Section: Discussionmentioning

confidence: 96%

Section: Fish Analysismentioning

confidence: 99%

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Fluorescence in situ hybridization, a diagnostic aid in ambiguous melanocytic tumors: European study of 113 cases

et al. 2011

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“…1 Although histological evaluation is a reliable means of accurately classifying melanocytic tumors as benign (nevi) or malignant (melanoma), this distinction can be difficult in a minority of cases. Based on the fact that melanomas are characterized by chromosomal aberrations, molecular genetic tests such as comparative genomic hybridization (CGH) [2][3][4] and fluorescence in situ hybridization [5][6][7][8] have been shown to be useful ancillary techniques, which assist accurate classification of melanocytic tumors. Multiple chromosomal gains and losses are identified with CGH in the majority (495%) of melanomas, whereas melanocytic nevi typically lack chromosomal aberrations.…”

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confidence: 99%

Histological and genetic evidence for a variant of superficial spreading melanoma composed predominantly of large nests

et al. 2012

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Cutaneous melanomas are characterized by a range of histological appearances, and several morphological variants have been described. In this study, we report a variant of superficial spreading melanoma that is characterized by large, irregular junctional melanocytic nests. The junctional nests varied in shape and size, showed focal tendency to confluence, and were often surrounded by a cuff of epidermal keratinocytes. The melanocytes comprising the nests showed variable cytological atypia. In most of the cases, scant intraepidermal or junctional single melanocytes were seen, and other well-documented diagnostic criteria for melanoma were lacking, and as a result, histological recognition of these tumors as melanoma was difficult. Some cases were associated with an invasive dermal component or showed evidence of sun damage. To provide supporting evidence for malignancy, we analyzed these tumors for genomic aberrations. Using array comparative genomic hybridization (aCGH), we identified multiple genomic aberrations in all analyzed cases. A similar pattern of genomic aberrations was seen in a control group of bona fide superficial spreading melanomas, suggesting that these 'melanomas composed exclusively or predominantly of large nests' are indeed variants of superficial spreading melanoma. Fluorescence in-situ hybridization (FISH) was positive in 40% of the cases. However, using aCGH, the FISH-negative cases showed multiple genomic aberrations in regions that are not covered by FISH. The low sensitivity of the FISH test can be explained by the fact that FISH only evaluates four genomic loci for aberrations, whereas aCGH surveys the entire genome. In summary, we present histological and molecular genetic evidence for a morphological variant of superficial spreading melanoma. Awareness of the histological features will aid in their correct diagnosis as melanoma, and in difficult cases, judicious application of ancillary tests such as aCGH (rather than FISH) will assist accurate diagnosis. Modern Pathology (2012) 25, 838-845; doi:10.1038/modpathol.2012; published online 2 March 2012 Keywords: chromosomal aberrations; comparative genomic hybridization; fluorescence in-situ hybridization; melanocytic tumors; melanoma Cutaneous melanomas are characterized by a diverse range of histological appearances, and several morphological variants have been described. The most common subtypes in histological classification systems are superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, and acral lentiginous melanoma. 1 Although histological evaluation is a reliable means of accurately classifying melanocytic tumors as benign

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“…The sensitivity and specificity of the FISH method varies dramatically among existing reports with the lesion subtype, the probe set used, the number of observers, and the cutoff thresholds used. Various authors have reported a FISH sensitivity ranging from 43% to 94% and a specificity ranging from 60% to 98% 24, 25, 26, 27, 28. The original 4‐probe FISH assay targeting 6p25 (RREB1), 6q23 (MYB), Cep6 (centromere 6), and 11q13 (CCND1) was reported to discriminate between histologically unequivocal melanomas and benign nevi with a sensitivity of 86.7% and a specificity of 95.4% 24.…”

Section: Discussionmentioning

confidence: 99%

An independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi

Clarke

Flake

Busam

et al. 2016

Cancer

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BACKGROUNDRecently, a 23‐gene signature was developed to produce a melanoma diagnostic score capable of differentiating malignant and benign melanocytic lesions. The primary objective of this study was to independently assess the ability of the gene signature to differentiate melanoma from benign nevi in clinically relevant lesions.METHODSA set of 1400 melanocytic lesions was selected from samples prospectively submitted for gene expression testing at a clinical laboratory. Each sample was tested and subjected to an independent histopathologic evaluation by 3 experienced dermatopathologists. A primary diagnosis (benign or malignant) was assigned to each sample, and diagnostic concordance among the 3 dermatopathologists was required for inclusion in analyses. The sensitivity and specificity of the score in differentiating benign and malignant melanocytic lesions were calculated to assess the association between the score and the pathologic diagnosis.RESULTSThe gene expression signature differentiated benign nevi from malignant melanoma with a sensitivity of 91.5% and a specificity of 92.5%.CONCLUSIONSThese results reflect the performance of the gene signature in a diverse array of samples encountered in routine clinical practice. Cancer 2017;123:617–628. © 2016 American Cancer Society.

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Fluorescence In Situ Hybridization (FISH) as an Ancillary Diagnostic Tool in the Diagnosis of Melanoma

Cited by 432 publications

References 33 publications

Fluorescence in situ hybridization, a diagnostic aid in ambiguous melanocytic tumors: European study of 113 cases

Fluorescence in situ hybridization, a diagnostic aid in ambiguous melanocytic tumors: European study of 113 cases

Histological and genetic evidence for a variant of superficial spreading melanoma composed predominantly of large nests

An independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi

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