Distinction of Desmoplastic Melanoma from Non-Desmoplastic Melanoma by Gene Expression Profiling

Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Journal of Investigative Dermatology (Impact Factor: 7.22). 03/2005; 124(2):412-8. DOI: 10.1111/j.0022-202X.2004.23600.x
Source: PubMed


Desmoplastic melanoma (DM) is a variant of melanoma characterized by the presence of amelanotic fusiform melanocytes dispersed in a prominent collagenous stroma. DM behaves differently from conventional non-desmoplastic melanoma (NDM). It has a higher tendency for local recurrence and is less likely to metastasize to regional lymph nodes. In this study, we explored the possibility of distinguishing DM from NDM by gene expression profiling. RNA samples from ten primary cutaneous melanomas of similar depth of invasion were analyzed using the Affymetrix U133A oligonucleotide platform. Four tumors were DM, five were ND, and one tumor showed combined features of desmoplastic and conventional. Hierarchical cluster analysis clearly separated DM from NDM. The expression of a number of melanocyte differentiation genes was decreased in DM compared with NDM, which corresponded to immunohistochemical results. Various genes were upregulated in DM, including neurotrophic factors and genes involved in extracellular matrix production. A novel finding was the high expression of clusterin in DM, which was confirmed by immunohistochemical studies. Our results from gene expression profiling validate the distinction of DM from NDM. They also provide the opportunity to learn more about the biology of DM which had previously not yet been associated with this variant of melanoma.

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Available from: Achim A Jungbluth, Mar 14, 2014
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    • "The natural progression of melanoma includes a multi-step pigmented nevus to melanoma transition. Several groups compared the transcriptomes of pigmented moles, primary melanomas and melanoma metastases [25-27]. The molecular mechanisms of melanoma progression were examined by comparative transcriptional profiling of melanoma metastases and melanoma cell lines vs. normal human melanocytes [28]. "
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    ABSTRACT: Recent years witnessed the birth of bioinformatics technologies, which greatly advanced biological research. These 'omics' technologies address comprehensively the entire genome, transcriptome, proteome, microbiome etc. A large impetus in development of bioinformatics was the introduction of DNA microarrays for transcriptional profiling. Because of its accessibility, skin was among the first organs analyzed using DNA microarrays, and dermatology among the first medical disciplines to embrace the approach. Here, DNA microarray methodologies and their application in dermatology and skin biology are reviewed. The most studied disease has been, unsurprisingly, melanoma; markers of melanoma progression, metastatic potential and even melanoma markers in blood have been detected. The basal and squamous cell carcinomas have also been intensely studied. Psoriasis has been comprehensively explored using DNA microarrays, transcriptional changes correlated with genomic markers and several signaling pathways important in psoriasis have been identified. Atopic dermatitis, wound healing, keloids etc. have been analyzed using microarrays. Noninvasive skin sampling for microarray studies has been developed. Simultaneously, epidermal keratinocytes have been the subject of many skin biology studies because they respond to a rich variety of inflammatory and immunomodulating cytokines, hormones, vitamins, UV light, toxins and physical injury. The transcriptional changes occurring during epidermal differentiation and cornification have been identified and characterized. Recent studies identified the genes specifically expressed in human epidermal stem cells. As dermatology advances toward personalized medicine, microarrays and related 'omics' techniques will be directly applicable to the personalized dermatology practice of the future.
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    • "CLU is implicated in diverse physiological functions including the regulation of cell growth and survival [12]. Its enhanced expression has been described in breast cancer [8], hepatocellular carcinoma [13], desmoplastic melanoma [14], colorectal cancer [15], bladder cancer [16], lymphomas [17] as well as ovarian cancer [18]. Multiple isoforms of CLU, arise from various post-translational modification processes, have been detected [19]. "
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    ABSTRACT: Acute-phase response involves the simultaneous altered expression of serum proteins in association to inflammation, infection, injury or malignancy. Studies of the acute-phase response usually involve determination of the levels of individual acute-phase serum proteins. In the present study, the acute-phase response of patients with epithelial (EOCa) and germ-line (GOCa) ovarian carcinoma was investigated using the gel-based proteomic approach, a technique which allowed the simultaneous assessment of the levels of the acute-phase serum high abundance proteins. Data obtained were validated using ELISA and immunostaining of biopsy samples. Enhanced expression of clusterin (CLU), alpha1-antitrypsin, haptoglobin and leucine rich glycoprotein was detected in all patients. However, the levels of alpha1-antichymotrypsin (ACT) was only enhanced in EOCa patients, while patients with GOCa were typically characterized by elevated levels of ceruloplasmin but lower levels of alpha2-HS glycoprotein. The enhanced expression of CLU in EOCa and GOCa patients and up-regulated expression of ACT specifically in EOCa patients were confirmed by ELISA. Immunohistochemical staining of biopsy samples of EOCa and GOCa patients demonstrated correlation of the acute-phase protein expression. Patients with EOCa and GOCa demonstrated distinctive aberrant expression of serum and tissue high abundance acute-phase proteins compared to negative control women.
    Proteome Science 07/2008; 6(1):20. DOI:10.1186/1477-5956-6-20 · 1.73 Impact Factor
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    ABSTRACT: Clusterin is an enigmatic protein altered in tumors of colo- rectal cancer patients. Because there is no information available about serum clusterin regarding this pathology, we applied proteomic techniques to analyze its isoforms in donors and patients. First we separated serum proteins through concanavalin A, obtaining a fraction with non- and O-glycosylated proteins (FI) and a second fraction enriched in N-glycoproteins (FII) wherein clusterin was supposed to elute on the basis of its glycosylation. Surprisingly analysis of the FI fraction revealed the existence of an unexpected and aberrantly N-glycosylated clusterin that was overex- pressed in patients and comprised at least five isoforms with different isoelectric points. On the other hand, two- dimensional electrophoretic analysis of the clusterin eluted in FII detected one isoform that was increased and 15 iso- forms that were decreased or absent in serum of patients. Finally immunoquantification by slot blot showed that in total serum and in FI the clusterin levels were significantly increased in patients, whereas in FII there was no signifi- cant variation. Therefore, serum clusterin and some of its isoforms could have a potential value as colorectal tumor markers and are interesting subjects for biomarker studies. Molecular & Cellular Proteomics 5:1647-1657, 2006.
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