Cyclin D1 Homogeneous Staining Regions by Fluorescent In Situ Hybridization: A Possible Indicator of Aggressive Behavior in Melanomas

Gerami, Pedram; Guitart, Joan; Martini, Mary C.; Wayne, Jeff D.; Kuzel, T.

doi:10.1001/archderm.144.9.1235-b

Cited by 7 publications

(6 citation statements)

References 5 publications

(6 reference statements)

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“…7 This assay looks for copy number gains in 11q13 (CCND1; alias Bcl-1) and imbalances in chromosome 6 with gains in the short arm at 6p25 (RREB1) and/or loss of the long arm at 6q23 (MYB). In the development of this assay, we previously published several original observations 8,9 linking high-level gains or amplification of CCND1 at 11q13 with poor prognosis in melanoma. Thus, in our extensive experience using FISH to evaluate chromosomal copy number aberrations in melanoma, we observed the following: i) melanomas are heterogeneous at the molecular level and may vary in the specific chromosomal aberrations present, and ii) specific copy number aberrations may have significant prognostic implications.…”

Section: Cancerorg/research/cancerfactsfigures/cancerfactsfigures/ Cmentioning

confidence: 99%

Copy Number Gains in 11q13 and 8q34 Are Highly Linked to Prognosis in Cutaneous Malignant Melanoma

Gerami

Jewell

Pouryazdanparast

et al. 2011

The Journal of Molecular Diagnostics

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Relating specific genetic alterations to prognosis may help improve prognostication in melanoma, may identify key oncogenic drivers in cancer, and may assist in developing targeted therapies. Characteristic genetic alterations in melanoma include chromosomal copy number aberrations. We evaluated 97 melanomas (55 metastasizing and 42 nonmetastasizing) after a minimum 5-year follow-up in a case-control study using fluorescence in situ hybridization, targeting commonly altered chromosomal loci in melanoma. Eight probes arranged in two panels were used, and 11 parameters were evaluated. Parameters showing a statistically significant difference between the metastasizing and nonmetastasizing groups were evaluated with multivariate logistic regression analysis to compare their prognostic potential with other traditional prognostic markers used by the American Joint Committee on Cancer. Four of 11 parameters evaluated, including CCND1 (alias Bcl-1) gain, CCND1 r-gain, MYC (alias c-myc) gain, and MYC r-gain, had a statistically significant difference in the metastasizing versus nonmetastasizing group. All four parameters maintained statistical significance when evaluated in separate multivariate logistic regression analyses that included the seven currently used American Joint Commission on Cancer prognosticators in melanoma. In multivariate analyses, these four parameters were second only to ulceration in their prognostic potential. Copy number changes at 11q13 and 8q34 harboring CCND1 and MYC, respectively, are highly associated with prognosis. Fluorescence in situ hybridization targeting these loci may be a useful standardized prognostic marker in melanoma skin cancer.

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Section: Cancerorg/research/cancerfactsfigures/cancerfactsfigures/ Cmentioning

confidence: 99%

Copy Number Gains in 11q13 and 8q34 Are Highly Linked to Prognosis in Cutaneous Malignant Melanoma

Gerami

Jewell

Pouryazdanparast

et al. 2011

The Journal of Molecular Diagnostics

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“…11 In this article, we report a total of 7 cases of aggressive melanomas, that in all demonstrated cyclin D1 HSR, providing further evidence to the possible prognostic implication of cyclin D1 HSR.…”

Section: Introductionmentioning

confidence: 60%

“…We had previously reported a case of aggressive melanoma in sun-damaged skin that demonstrated prominent HSR for CCND1. 11 At that time, we had postulated that HSR for CCND1 may portend a worse prognosis, based on the aggressive clinical course of the reported patient. In the present work, we have compiled 6 additional cases of melanoma with HSRs, of which 5 have clinical follow-up available and have shown an aggressive clinical course.…”

Section: Discussionmentioning

confidence: 96%

“…One case had previously been reported. 11 Whenever possible, demographic information, clinical and pathologic staging information, and any clinical follow up was collected from the chart.…”

Section: Methodsmentioning

confidence: 99%

“…[2][3][4][5][6][7][8][9][10] More recently, several studies have suggested that specific chromosomal aberrations may also serve as prognostic markers in cases of unequivocal melanoma. [11][12][13] Specifically, we have noted in previous studies that high-level gains of cyclin D1(CCND1) located at 11q13 is linked with poor prognosis.…”

Section: Introductionmentioning

confidence: 99%

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Homogeneous Staining Regions for Cyclin D1, a Marker of Poor Prognosis in Malignant Melanoma

Gammon¹,

Guitart²,

Gerami³

2012

The American Journal of Dermatopathology

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Homogeneous staining regions (HSRs) have been previously shown to confer a worse prognosis in solid tumors and myelodysplastic syndromes. We previously reported a single case of melanoma with HSR for cyclin D1 and postulated that HSR for cyclin D1 is an independent poor prognostic indicator. Herein, we report 7 cases of melanoma with HSR for cyclin D1. The cases occurred in elderly men and women with an average age of 65 years. Three cases occurred in areas of intermittent sun exposure, 2 cases occurred in chronically sun-damaged areas, and 2 cases were acral. HSR correlated with aggressive histology. The average Breslow depth was 2.7 mm (range, 1-11 mm), the average mitotic index was 5.1 per square millimeter, and 5 of the 7 cases were ulcerated. Clinical follow-up was available for 6 of the 7 cases. Five of the 6 cases for which clinical follow-up was available metastasized, and 1 patient died of metastatic melanoma. Three cases with metastatic disease occurred in primary melanomas with lower Breslow depths, ranging from 1.0 to 1.4 mm. These additional cases of melanoma with an aggressive clinical course provide further evidence of the prognostic significance of HSR for cyclin D1 in melanoma. Larger cohort studies are needed to validate this observation.

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Technologies in the Molecular Diagnostics Laboratory

Elaba

Murphy²,

Mnayer³

2011

Molecular Diagnostics in Dermatology and Dermatopathology

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Cyclin D1 Homogeneous Staining Regions by Fluorescent In Situ Hybridization: A Possible Indicator of Aggressive Behavior in Melanomas

Cited by 7 publications

References 5 publications

Copy Number Gains in 11q13 and 8q34 Are Highly Linked to Prognosis in Cutaneous Malignant Melanoma

Copy Number Gains in 11q13 and 8q34 Are Highly Linked to Prognosis in Cutaneous Malignant Melanoma

Homogeneous Staining Regions for Cyclin D1, a Marker of Poor Prognosis in Malignant Melanoma

Technologies in the Molecular Diagnostics Laboratory

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