Chromogenic <i>in situ</i> hybridization analysis of melastatin mRNA expression in melanomas from American Joint Committee on Cancer stage I and II patients with recurrent melanoma

Hammock, Lauren; Cohen, Cynthia; Carlson, Grant W.; Murray, David; Ross, Jeffrey S.; Sheehan, Christine E.; Nazir, Talat M.; Carlson, John A.

doi:10.1111/j.1600-0560.2006.00501.x

Cited by 35 publications

(37 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These genes, which are associated with normal melanocyte differentiation, were recently identified as part of a transcriptional signature that is lost in aggressive melanomas compared with normal melanocytes (45), supporting a model in which the loss of Wnt/ß-catenin-regulated genes is associated with both de-differentiation and melanoma progression. Consistent with this hypothesis, the loss of TRPM1 has been linked to decreased survival and increased risk of metastasis (46)(47)(48), and the ability of Wnt/ß-catenin signaling to rescue the transcriptional regulation of TRPM1 and other genes lost with melanoma progression provides further evidence that loss of Wnt/ß-catenin homeostasis may play a direct role in melanoma progression. Our findings also suggest that WNT5A, which is expressed at higher levels with melanoma progression (21)(22)(23)(24), may directly contribute to this dysregulation by antagonizing Wnt/ß-catenin transcriptional targets.…”

Section: Discussionsupporting

confidence: 53%

Activated Wnt/ß-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model

Chien

Moore

Lonsdorf

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

318

319

View full text Add to dashboard Cite

This study demonstrates that in malignant melanoma, elevated levels of nuclear ß-catenin in both primary tumors and metastases correlate with reduced expression of a marker of proliferation and with improved survival, in contrast to colorectal cancer. The reduction in proliferation observed in vivo is recapitulated in B16 murine melanoma cells and in human melanoma cell lines cultured in vitro with either WNT3A or small-molecule activators of ß-catenin signaling. Consistent with these results, B16 melanoma cells expressing WNT3A also exhibit decreased tumor size and decreased metastasis when implanted into mice. Genome-wide transcriptional profiling reveals that WNT3A up-regulates genes implicated in melanocyte differentiation, several of which are down-regulated with melanoma progression. These findings suggest that WNT3A can mediate transcriptional changes in melanoma cells in a manner reminiscent of the known role of Wnt/ß-catenin signaling in normal melanocyte development, thereby altering melanoma cell fate to one that may be less proliferative and potentially less aggressive. Our results may explain the observed loss of nuclear ß-catenin with melanoma progression in human tumors, which could reflect a dysregulation of cellular differentiation through a loss of homeostatic Wnt/ß-catenin signaling.differentiation ͉ prognosis ͉ metastasis ͉ WNT5A ͉ B16 model ͉ microarray M alignant melanoma accounts for Ͻ5% of all skin cancers, yet is responsible for 80% of skin cancer deaths (1). The outlook for patients with metastatic melanoma remains quite bleak, with a 5-year survival rate of only 5%-15% that has not changed significantly over decades despite intensive efforts to develop an effective therapy. Although the molecular mechanisms underlying the formation and progression of melanoma remain unresolved, recent studies have implicated Wnt signal transduction pathways in melanoma biology (2), raising the question of whether this insight can be used to develop a therapy.

show abstract

Section: Discussionsupporting

confidence: 53%

Activated Wnt/ß-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model

Chien

Moore

Lonsdorf

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

318

319

View full text Add to dashboard Cite

show abstract

“…Ulceration was identified in 1 of 95 Spitz nevi and in 14 of the 33 nodular melanomas. Mitotic activity was identified in 22 of 95 of the [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Of the 33 patients with nodular malignant melanoma, 17 did not experience metastasis, 5 patients were alive but had suffered metastases, and 11 patients died from complications related to metastatic melanoma.…”

Section: Resultsmentioning

confidence: 99%

“…[8][9][10][11] TRPM1 is a member of the transient receptor potential (TRP) channel family with as-yet determined function in melanocytic tumors. Channels in the TRP family allow for calcium entry into cells, producing intracellular responses linked to the phosphatidylinositol and protein kinase C signal transduction pathways.…”

mentioning

confidence: 99%

TRPM1 (Melastatin-1/MLSN1) mRNA expression in Spitz nevi and nodular melanomas

et al. 2009

View full text Add to dashboard Cite

The transient receptor potential cation channel, subfamily M, member 1 (TRPM1/Melastatin-1/MLSN-1) expression has been shown to have prognostic utility in the evaluation of primary cutaneous melanoma. We analyzed a series of spindled and epithelioid cell nevi (Spitz) and primary cutaneous nodular melanomas to determine whether the expression of TRPM1 mRNA may be useful in distinguishing between Spitz nevi and nodular melanomas and to further examine the patterns of TRPM1 mRNA expression in cutaneous melanocytic proliferations. Formalin-fixed, paraffin-embedded tissues from 95 Spitz nevi and 33 nodular melanomas were analyzed for the expression of TRPM1 mRNA by in situ hybridization using 35 S-labeled riboprobes. Ubiquitous melanocytic expression of TRPM1 mRNA was observed in 56 of 95 (59%) Spitz nevi and 4 of 33 (12%) nodular melanomas. Diffusely scattered loss of TRPM1 mRNA was identified in 38 of 95 (40%) Spitz nevi and 2 of 33 (6%) nodular melanomas. Regional loss of the TRPM1 mRNA expression by a significant subset of dermal tumor cells or a complete absence of TRPM1 expression by the dermal tumor was identified in 27 of 33 (82%) nodular melanomas, but only 1 of 95 (1%) Spitz nevi. These findings suggest that the pattern of TRPM1 mRNA expression may be helpful in the differentiation of Spitz nevi and nodular melanomas. Of the 16 patients who experienced metastasis, 15 (94%) had primary tumors that displayed reduced MLSN mRNA expression by all or a part of the dermal tumor.

show abstract

“…Parallel zu diesen technischen Optimierungen erweiterte sich das Anwendungsspektrum der ISH von dem Nachweis ursprünglich einer einzelnen Nukleinsäure-sequenz hin zu multiplen Genzielen, die in einem einzigen Versuchsansatz nachgewiesen werden können. Durch die Verwendung mehrerer spektral unterschiedlicher Fluorochrome können über eine computerbasierte Verhältnisanalyse der detektierten Farbspektren mehrere genetische Ziele parallel analysiert werden (M-FISH, SKY, COBRA), beispielsweise alle 24 Chromosomen in einem Hybridisierungsansatz [17]. Die Indikationen für ISH, FISH, CISH etc.…”

Section: Introductionunclassified

Molekulargenetik in der dermatologischen Diagnostik

Braun‐Falco

Ruzicka

2012

Hautarzt

View full text Add to dashboard Cite

Modern molecular techniques have tremendously expanded our knowledge about the biologic processes in healthy individuals as well as our understanding about the pathologic events in an increasing number of dermatological diseases. These technologies initially came from basic molecular biology and genetic research but have become firmly anchored in clinical diagnosis approaches. Included in this group are immunohistochemistry (IHC), polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), chromogen in situ hybridization (CISH), comparative genomic hybridization (CGH), and microarray technology. IHC and PCR already belong to the armamentarium for routine daily diagnostics due to their high degree of standardization and reproducibility, ease of use and relatively low costs. Others like FISH and CISH are currently employed for specific indications in a growing number of larger laboratories, whereas CGH and microarray technology still remain in the hands of a few highly specialized laboratories. These new ancillary methods will help to improve diagnostic accuracy particularly in cases in which conventional histopathology is ambiguous. In addition, they will provide new and important information concerning the prognosis, progression and response rate to therapies in several particular malignant diseases.

show abstract

Chromogenic in situ hybridization analysis of melastatin mRNA expression in melanomas from American Joint Committee on Cancer stage I and II patients with recurrent melanoma

Abstract: Extensive loss of MLSN in PM correlated with aggressive metastatic melanoma. Ancillary testing for MLSN mRNA expression by CISH could offer a means to more accurately identify AJCC stage I and II patients at risk for metastatic disease, who could benefit from adjuvant therapy.

Cited by 35 publications

References 27 publications

Activated Wnt/ß-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model

Activated Wnt/ß-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model

TRPM1 (Melastatin-1/MLSN1) mRNA expression in Spitz nevi and nodular melanomas

Molekulargenetik in der dermatologischen Diagnostik

Contact Info

Product

Resources

About