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      Immunohistochemical detection of Hsp90 and Ki-67 in pterygium

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          Abstract

          Background

          To examine the immunohistochemical expression of heat shock protein 90 (Hsp90) and Ki-67 protein in human pterygium.

          Materials and methods

          Tissues obtained during pterygium surgery of 15 patients who underwent the bare-sclera procedure and 10 normal conjunctivae were studied. All of these pterygia were primary ones. Recurrent pterygia were excluded. Normal bulbar conjunctivas (2 x 2 mm) were obtained from the nasal region close to the limbus from patients during their cataract and retina surgeries. Immunohistochemical detection of Hsp90 and Ki67 was done using the streptavidin–biotin method in paraffin embedded tissue sections.

          Results

          The percentage of cells stained for Hsp90 was greater for pterygium epithelium (76 ± 10.8) than for normal conjunctiva (1.4 ± 0.8). In each pterigyum sample more than 60% of cells were positive. The differences in positive cells between normal and pterigyum epithelium were highly significant for Hsp90 (P < 0,001).

          Pterygium epithelium also showed a higher percentage of cells that stained for Ki67 (10.1 ± 9.5) than for normal conjunctiva (2.1 ± 1.9). The differences in positive cells were also statistically significant for Ki67 (P < 0.01). Although there were significant differences in the majority of samples observed. It was noted that in some samples there was no difference between normal and pterygium epithelium for Ki67.

          Conclusion

          Our results indicate an abnormal expression of Hsp90 and ki-67 in pterygium samples when compared to normal conjunctiva.The finding of abnormal expression of levels of Hsp90 in pterygium samples can stimulate new research into pterygium and its recurrence.

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          The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1128478792898812

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          Most cited references41

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          Heat shock proteins in cancer: chaperones of tumorigenesis.

          The heat shock proteins (HSPs) induced by cell stress are expressed at high levels in a wide range of tumors and are closely associated with a poor prognosis and resistance to therapy. The increased transcription of HSPs in tumor cells is due to loss of p53 function and to higher expression of the proto-oncogenes HER2 and c-Myc, and is crucial to tumorigenesis. The HSP family members play overlapping, essential roles in tumor growth both by promoting autonomous cell proliferation and by inhibiting death pathways. The HSPs have thus become targets for rational anti-cancer drug design: HSP90 inhibitors are currently showing much promise in clinical trials, whereas the increased expression of HSPs in tumors is forming the basis of chaperone-based immunotherapy.
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            Heat-shock protein 90, a chaperone for folding and regulation.

            D Picard (2002)
            Heat-shock protein 90 (Hsp90) is an abundant and highly conserved molecular chaperone that is essential for viability in eukaryotes. Hsp90 fulfills a housekeeping function in contributing to the folding, maintenance of structural integrity and proper regulation of a subset of cytosolic proteins. A remarkable proportion of its substrates are proteins involved in cell cycle control and signal transduction. Hsp90 acts with a cohort of Hsp90 co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. The large conformational flexibility of Hsp90 and a multitude of dynamic co-chaperone complexes contribute to generating functional diversity, and allow Hsp90 to assist a wide range of substrates.
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              Functional proteomic screens reveal an essential extracellular role for hsp90 alpha in cancer cell invasiveness.

              Tumour cell invasiveness is crucial for cancer metastasis and is not yet understood. Here we describe two functional screens for proteins required for the invasion of fibrosarcoma cells that identified the molecular chaperone heat shock protein 90 (hsp90). The hsp90 alpha isoform, but not hsp90 beta, is expressed extracellularly where it interacts with the matrix metalloproteinase 2 (MMP2). Inhibition of extracellular hsp90 alpha decreases both MMP2 activity and invasiveness. This role for extracellular hsp90 alpha in MMP2 activation indicates that cell-impermeant anti-hsp90 drugs might decrease invasiveness without the concerns inherent in inhibiting intracellular hsp90.
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                Author and article information

                Journal
                Diagn Pathol
                Diagn Pathol
                Diagnostic Pathology
                BioMed Central
                1746-1596
                2013
                21 February 2013
                : 8
                : 32
                Affiliations
                [1 ]Department of Ophthalmology, Universitary Hospital Federal Fluminense University, Rio de Janeiro, Brazil
                [2 ]Henry C. Witelson Ocular Pathology Laboratory, McGill University, Montreal, Canada
                Article
                1746-1596-8-32
                10.1186/1746-1596-8-32
                3599841
                23432803
                eed5e548-d37b-4a0d-93ca-567b8b67c8cf
                Copyright ©2013 Sebastiá et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 January 2013
                : 17 February 2013
                Categories
                Research

                Pathology
                hsp90,immunohistochemistry,ki-67,pterygium
                Pathology
                hsp90, immunohistochemistry, ki-67, pterygium

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