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Zinc-based fixative improves preservation of genomic DNA and proteins in histoprocessing of human tissues
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
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2003 In: Laboratory Investigation, Vol. 83, no 6, 889-899 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2003. Vol. 83, no 6, 889-899 p.
URN: urn:nbn:se:uu:diva-93047OAI: oai:DiVA.org:uu-93047DiVA: diva2:166405
Available from: 2005-05-11 Created: 2005-05-11Bibliographically approved
In thesis
1. Molecular Analysis of Normal Human Skin and Basal Cell Carcinoma Using Microdissection Based Methods
Open this publication in new window or tab >>Molecular Analysis of Normal Human Skin and Basal Cell Carcinoma Using Microdissection Based Methods
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this thesis was to gain further insight into the biology of normal human skin and basal cell carcinoma (BCC). Morphology in combination with microdissection was used as primary tool for sampling.

Using the X-chromosome inactivation assay, we found normal human skin to consist of a mosaic of cells, with either the maternal or the paternal X-chromosome inactivated. We believe that each tile is made up of several epidermal proliferative units with identical X-chromosome inactivation patterns. Using the same method, we found BCC to be a monoclonal neoplasm imbedded in polyclonal stroma. However, one tumor displayed clear evidence of being composed of two intermingled monoclonal tumors.

To better enable molecular analysis of defined cells from tissue sections, we investigated a zinc-based fixative as alternative to neutral-buffered formalin. Zinc-based fixative preserves good quality of genomic DNA, with only slight impairment of morphology. In addition, it partly abrogates the need for antigen retrieval.

The patched gene is involved in BCC development. We analyzed the distribution of a coding polymorphism (Pro/Leu) at codon 1315 in populations with different skin types. We found a reduced Pro/Pro genotype frequency in populations with lighter pigmentation. This in combination with genotype analyses of patients with multiple BCCs, showed that failure to lose the Pro allele during a shift towards lighter pigmented skin may be associated with an increased risk of developing BCC.

We compared the expression profile of BCC cells with putative progenitor cells in the basal layer of epidermis. In addition to discovering several unknown genes, we found the Wnt signaling pathway to upregulated. Furthermore, differentiation markers were downregulated together with proteins important for scavenging of oxygen radicals.

In conclusion, the combination of morphology, microdissection and subsequent molecular applications provided valid information deepening our understanding of normal skin and BCC.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 50 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 40
Pathology, skin, basal cell carcinoma, microdissection, X-chromosome inactivation, Patologi
National Category
Cell and Molecular Biology
urn:nbn:se:uu:diva-5795 (URN)91-554-6249-9 (ISBN)
Public defence
2005-05-28, Rudbecksalen, Rudbecklaboratoriet C11, Dag Hammarskjöldsväg 20, Uppsala, 09:15
Available from: 2005-05-11 Created: 2005-05-11Bibliographically approved

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