Fluorescence in Situ Hybridization for Distinguishing Nevoid Melanomas From Mitotically Active Nevi

Gerami, Pedram; Wass, Amanda B.; Mafee, Mariam; Fang, Yuaquin; Pulitzer, Melissa; Busam, Klaus J.

doi:10.1097/pas.0b013e3181ba6db6

Cited by 129 publications

(92 citation statements)

References 12 publications

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“…21 It could also be useful if it really changes the treatment of patients, for example, with a thickness greater than 1 or 1.5 mm (according to the protocol), leading to interferon treatment or other adjuvant management such as sentinel node biopsy or adjuvant vaccine therapy. Other FISH applications have been reported to facilitate the differential diagnosis between (I) epithelioid blue nevus and cutaneous metastatic melanoma simulating blue nevus 22 or (ii) nevoid melanomas and mitotically active nevi, 23 (iii) conjunctival nevi from melanomas 24 or (iv) intranodal nevus from metastatic melanoma. 25 In conclusion, a single genetic test allowing the differential diagnosis between benign and malignant ambiguous melanocytic lesions does not yet exist.…”

Section: Discussionmentioning

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: Discussionmentioning

confidence: 99%

“…The aims of our study were first to perform FISH analysis in 43 cases of non-equivocal melanomas (23) and nevi (20) in a training set. Then, we analyzed 113 cases of ambiguous melanocytic tumors provided by six European centers to determine the relevance of such testing by comparison with an expert panel review as well as with patients' clinical course.…”

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confidence: 99%

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

et al. 2011

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“…6 Several proof-of-principle studies showed potential applications of FISH to solve a variety of diagnostic dilemmas in the evaluation of melanocytic tumors, including differentiating blue nevus-like metastasis from blue nevus, mitotically active nevus from nevoid melanoma, and dysplastic nevus from superficial spreading melanoma. [7][8][9][10][11][12] Fluorescence in situ hybridization test abnormalities characteristic of melanoma were identified in lentiginous melanoma supporting this entity as a variant of melanoma.…”

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confidence: 99%

Correlation Between Histologic Assessment and Fluorescence In Situ Hybridization Using MelanoSITE in Evaluation of Histologically Ambiguous Melanocytic Lesions

Zembowicz

Yang²,

Kafanas

et al. 2012

Archives of Pathology & Laboratory Medicine

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N Context.-The 4-probe, multicolor, fluorescence in situ hybridization (FISH) panel targeting chromosomes 6 and 11 has shown promising sensitivity and specificity in distinguishing between benign nevi and malignant melanoma. Only a few studies have assessed the potential utility of FISH in classification of histologically ambiguous melanocytic lesions. In the United States, this assay is exclusively licensed to NeoGenomics Laboratories (Irvine, California), which provides the technical component and has developed an innovative service (MelanoSITE) allowing pathologists to interpret FISH results using a dedicated Web portal. Thus far, use of MelanoSITE as a diagnostic adjunct in the diagnosis of melanocytic lesions has not, to our knowledge, been reported in the literature.Objective.-To analyze 1.5 years of experience with the MelanoSITE melanoma FISH assay in the evaluation of histologically ambiguous lesions in the context of second opinion and routine dermatopathology practice.Design.-A prospective histologic/FISH correlation study of 140 cases.Results.-Twenty-seven percent of abnormal FISH results were false-positive results because of tetraploidy. After correcting for known false-positive results, all lesions considered atypical nevi showed normal FISH signals. Abnormal FISH signals were reported in 30% of lesions considered histologically borderline and in 48% of lesions in which a diagnosis of melanoma was favored.Conclusions.-Four-probe, multicolor FISH results for melanoma correlate with the microscopic assessments of histologically ambiguous lesions. Pathologists using MelanoSITE must be aware of the high rate of false-positive results from tetraploidy.

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“…24 Finally, the human RREB1 locus has been found to be amplified in melanoma and is currently an area of intense investigation for its potential in molecular diagnostic testing. [25][26][27][28][29][30] In prostate cancer, RREB1 binds the PSA promoter only in association with AR to repress transcription. 20 In summary, the current literature on RREB1 suggests con-text-dependent phenotypes that may suppress or promote carcinogenesis and tumor progression.…”

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confidence: 99%

RREB1 Transcription Factor Splice Variants in Urologic Cancer

Nitz

Harding

Smith

et al. 2011

The American Journal of Pathology

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RREB1 is an alternatively spliced transcription factor implicated in Ras signaling and cancer. Little is known about the expression of RREB1 isoforms in cell lines or human tumors, or about the clinical relevance of the latter. We have developed tools for IHC of RREB1 protein isoform-specific amplification of RREB1 mRNA and selective knockdown of RREB1 isoforms and use these to provide new information by characterizing RREB1 expression in bladder and prostate cancer cell lines and human tissue samples. Previously described splice variants RREB1␣, RREB1␤, RREB1␥, and RREB1␦ were identified, as well as the novel variant RREB1 . Total and isoform-specific mRNA expression was lower in most but not all tumors, compared with normal tissues. RREB1 IHC performed on a bladder cancer TMA did not indicate a relationship between total RREB1 expression and overall survival after radical cystectomy for invasive bladder cancer. In contrast, in vitro proliferation studies using the UMUC-3 bladder cancer cell line after selective isoform-specific knockdown of expression indicate that RREB1␣ is not necessary for proliferation, but that RREB1␤ may be required. These contributions should accelerate progress in the nascent RREB1 field by providing new reagents while also providing clues to the role of RREB1 isoforms in human cancer and raising the possibility of isoform-specific roles in human carcinogenesis and progression.

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Fluorescence in Situ Hybridization for Distinguishing Nevoid Melanomas From Mitotically Active Nevi

Cited by 129 publications

References 12 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

Correlation Between Histologic Assessment and Fluorescence In Situ Hybridization Using MelanoSITE in Evaluation of Histologically Ambiguous Melanocytic Lesions

RREB1 Transcription Factor Splice Variants in Urologic Cancer

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