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The protein expression of TRP-1 and galectin-1 in cutaneous malignant melanomas
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2008 (English)In: Cancer Genomics & Proteomics, ISSN 1109-6535, E-ISSN 1790-6245, Vol. 5, no 6, 293-300 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Patients with metastazing malignant melanoma have a poor outcome and determination of thickness of the primary tumor remains as the most important prognostic predictor. The aim of this study was to use an antibody-based proteomics strategy to search for new molecular markers associated with melanoma progression. Two proteins, TRP-1 and galectin-1, were identified as proteins with enhanced expression in cells from the melanocytic lineage. PATIENTS AND METHODS: Protein profiling of TRP-1 and galectin-1 together with proliferation marker Ki-67 and melanocyte marker Melan-A was performed in normal tissues from 144 individuals and in 216 different tumors using tissue microarrays and immunohistochemistry. The protein expression pattern was further analyzed in a defined cohort of 157 patients diagnosed with invasive cutaneous malignant melanoma. RESULTS: Both TRP-1 and galectin-1 were highly expressed in normal melanocytes and melanoma. The expression of TRP-1 was inversely correlated with tumor stage (p=0.002, (R=-0.28)). Neither TRP-1 or galectin-1 was associated with overall or disease free survival (p>0.14, p>0.46 respectively). Ki-67 was associated with tumor stage and survival (p<0.001). CONCLUSION: TRP-1 and galectin-1 protein expression patterns were determined in normal and cancer tissues and both proteins were expressed in the majority of the malignant melanomas. There was no correlation between TRP-1 or galectin-1 expression and survival.

Place, publisher, year, edition, pages
2008. Vol. 5, no 6, 293-300 p.
Keyword [en]
human Protein Atlas Program, malignant melanoma, TRP-1, galectin-1
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-105314PubMedID: 19287070OAI: oai:DiVA.org:uu-105314DiVA: diva2:221076
Available from: 2009-06-03 Created: 2009-06-03 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Prognostic Factors in Malignant Melanoma
Open this publication in new window or tab >>Prognostic Factors in Malignant Melanoma
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Because of the failure so far to find effective treatment for patients with advanced stages of melanoma, increasing efforts have been made to find prognostic factors identifying patients in the risk zone for development of metastasis.

This thesis investigates the prognostic powers of a few selected serological and immunohistochemical biomarkers.

In the first and second study, patients operated on for localized malignant melanoma were investigated regarding the prognostic impact of angiogenic serological markers and circulating levels of S100. We concluded that the S100 assays, especially S100BB, are potential biomarkers in patients with malignant melanoma, correlated to both survival and disease free survival. However, no such conclusion could be drawn from the first study, where we found no correlation to survival and investigated angiogenic markers.

In the third and fourth study four new potential immunohistochemical biomarkers where investigated in collaboration with the Swedish Human Protein Atlas Program, and those where TRP-1, galectin-1, DLG5 and syntaxin-7.

We found that TRP-1 correlated inversely with tumor stage and galectin-1 correlated to Ki-67.

DLG5 showed a significant inverse correlation to Ki67 and the expression of STX7 was inversely correlated to tumor stage, suggesting that decreased expression is associated with more aggressive tumors.

None of the investigated markers in study III and IV correlated with disease free survival or overall survival.

In the fifth and last study, we examined the expression of SOX10, a transcription factor, in different melanocytic lesions. Also, a proliferation assay was carried out in a human melanoma cell line. The results reveal the presence of SOX10 in different melanocytic lesions, with a weak inverse correlation to survival and a significant inverse correlation to T-stage. A significant decrease in proliferation rate for SOX10 silenced cells was found and our data also suggests an increased migratory response in SOX10 silenced cells.

Place, publisher, year, edition, pages
Uppsala: Universitetsbiblioteket, 2008. 69 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 410Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 410
Keyword
Malignant melanoma, prognostic factors, survival, chemotherapy, radiation
Identifiers
urn:nbn:se:uu:diva-9511 (URN)978-91-554-7378-5 (ISBN)
Public defence
2009-01-16, Skoog Salen, Onkologkliniken, ing 78, Uppsala Universitetssjukhus, 751 85, Uppsala, 09:15
Opponent
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Available from: 2008-12-22 Created: 2008-12-22 Last updated: 2013-06-20Bibliographically approved

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PubMedhttp://cgp.iiarjournals.org/content/5/6/293.long

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Agnarsdóttir, MargrétPontén, FredrikBergqvist, Michael

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