Chromosomal Aberrations by 4-Color Fluorescence In Situ Hybridization Not Detected in Spitz Nevi of Older Individuals
OBJECTIVE To investigate whether Spitz nevi with typical histopathological features in older patients demonstrate chromosomal aberrations by 4-color fluorescence in situ hybridization (FISH). DESIGN Retrospective medical record review, with prospective masked histopathological and cytogenetic analyses. SETTING University-affiliated dermatology and dermatopathology setting. PATIENTS Twenty-five patients 50 years or older with melanocytic nevi showing histopathological features typical of Spitz nevi. MAIN OUTCOME MEASURES Three dermatopathologists masked to the patients' ages reviewed histopathological sections of melanocytic lesions for features typical of Spitz nevi. FISH was performed on samples with typical histopathological features by a 4-color FISH probe set used for the evaluation of malignant melanocytic neoplasms. RESULTS None of the study cases showing histopathological features typical of Spitz nevi had detectable chromosomal abnormalities by FISH. CONCLUSIONS Spitz nevi in older patients demonstrate molecular features similar to those of Spitz nevi in younger age groups. The findings of normal karyotypes in combination with typical histopathological features are reassuring of Spitz nevus diagnoses in older patients and suggest no correlation of increased malignant potential with advanced age per se.
Available from: Tao Cheng
- "Most primary melanomas exhibit either numerical or structural chromosomal abnormalities, such as deletions in 9p, 10, 6q and 8p and copy-number increase in 7, 8, 6p, 1q, 20, 17, and 2 [75,76]. Given that multiple chromosomal aberrations must be evaluated to obtain genetic profiles of melanoma, a multi-color approach comprising 4 gene probes have been adopted for a FISH-based melanoma assay . The clinical studies showed that use of FISH in unambiguous cases provided promising results with relatively high sensitivity and specificity. "
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ABSTRACT: Extensive studies of the genetic aberrations related to human diseases conducted over the last two decades have identified recurrent genomic abnormalities as potential driving factors underlying a variety of cancers. Over the time, a series of cutting-edge high-throughput genetic tests, such as microarrays and next-generation sequencing, have been developed and incorporated into routine clinical practice. Although it is a classical low-throughput cytogenetic test, fluorescence in situ hybridization (FISH) does not show signs of fading; on the contrary, it plays an increasingly important role in detecting specific biomarkers in solid and hematologic neoplasms and has therefore become an indispensable part of the rapidly developing field of personalized medicine. In this article, we have summarized the recent advances in FISH application for both de novo discovery and routine detection of chromosomal rearrangements, amplifications, and deletions that are associated with the pathogenesis of various hematopoietic and non-hematopoietic malignancies. In addition, we have reviewed the recent developments in FISH methodology as well.
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ABSTRACT: The diagnosis of Spitz nevus in an elderly individual is often met with skepticism because the lesion can be difficult to distinguish from melanoma and because the probability of a malignant melanoma is higher in older patients. Recently, increased sensitivity for detection of malignant spitzoid neoplasms using 9p21 fluorescence in situ hybridization (FISH) has been described. In this study, we address the question of whether histopathologically typical Spitz nevi occurring in patients 50 years and older show any abnormalities regarding the 9p21 CDKN2A tumor suppressor gene locus. p16 immunohistochemistry (IHC), as well as dual-color FISH for assessment of diploid or hypodiploid status at 9p21, was performed in 25 classic Spitz nevi from patients 50 years and older and was compared with findings in a younger control population. All cases of typical Spitz nevi occurring in older patients retained p16 expression by immunohistochemistry and showed normal, diploid 9p21 FISH signals. Heterozygous loss of 9p21 by FISH was noted in a control case of a 9-year-old girl and is of unknown significance. These findings indicate that p16 expression by immunohistochemistry in classic Spitz nevi correlates well with absence of malignancy-associated cytogenetic abnormalities at 9p21 by FISH independent of the patient's age. Assessment of p16 expression by standard immunohistochemistry may therefore be reassuring in routine clinical practice when the patient is of advanced age, and can be helpful as a screening tool to select IHC-negative cases for extended FISH analysis targeting the 9p21 gene locus.
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ABSTRACT: Fluorescent in situ hybridization (FISH) and comparative genomic hybridization (CGH) are molecular techniques that have become valuable adjuncts in the diagnosis of histopathologically ambiguous melanocytic tumors. These techniques detect the presence of chromosomal gains or losses that are characteristic of malignant transformation in melanocytic neoplasms. CGH and FISH have been used to characterize distinct genomic characteristics of melanocytic tumors at various anatomic sites and tumors with certain histopathologic features (e.g. spitzoid, blue nevus-like, congenital nevi). Recent developments in this field include the transition of CGH from a research tool to a clinically available test and a new FISH probe set targeting chromosomal loci 11q13, 8q24, 6p25 and 9p21 that reportedly distinguishes melanoma from melanocytic nevi with a sensitivity and specificity of 94% and 98% respectively. Genomic analysis of melanocytic tumors also provides prognostic information. This review discusses these new advances in molecular diagnostics in melanoma and future directions in the field.
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