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  • 1. Lindgren, David
    et al.
    Frigyesi, Attila
    Gudjonsson, Sigurdur
    Sjödahl, Gottfrid
    Halldén, Christer
    Department of Laboratory Medicine, Clinical Chemistry, Malmö University Hospital.
    Chebil, Gunilla
    Veerla, Srinivas
    Ryden, Tobias
    Månsson, Wiking
    Liedberg, Fredrik
    Höglund, Mattias
    Combined gene expression and genomic profiling define two intrinsic molecular subtypes of urothelial carcinoma and gene signatures for molecular grading and outcome2010In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 70, no 9, p. 3463-3472Article in journal (Refereed)
    Abstract [en]

    In the present investigation, we sought to refine the classification of urothelial carcinoma by combining information on gene expression, genomic, and gene mutation levels. For these purposes, we performed gene expression analysis of 144 carcinomas, and whole genome array-CGH analysis and mutation analyses of FGFR3, PIK3CA, KRAS, HRAS, NRAS, TP53, CDKN2A, and TSC1 in 103 of these cases. Hierarchical cluster analysis identified two intrinsic molecular subtypes, MS1 and MS2, which were validated and defined by the same set of genes in three independent bladder cancer data sets. The two subtypes differed with respect to gene expression and mutation profiles, as well as with the level of genomic instability. The data show that genomic instability was the most distinguishing genomic feature of MS2 tumors, and that this trait was not dependent on TP53/MDM2 alterations. By combining molecular and pathologic data, it was possible to distinguish two molecular subtypes of T(a) and T(1) tumors, respectively. In addition, we define gene signatures validated in two independent data sets that classify urothelial carcinoma into low-grade (G(1)/G(2)) and high-grade (G(3)) tumors as well as non-muscle and muscle-invasive tumors with high precisions and sensitivities, suggesting molecular grading as a relevant complement to standard pathologic grading. We also present a gene expression signature with independent prognostic effect on metastasis and disease-specific survival. We conclude that the combination of molecular and histopathologic classification systems might provide a strong improvement for bladder cancer classification and produce new insights into the development of this tumor type.

  • 2.
    Tassidis, Helena
    et al.
    Lund University.
    Brokken, Leon
    Ulmert, David
    Ehrnström, Roy
    Jirström, Karin
    Bjartell, Anders
    Härkönen, Pirkko
    Gjörloff Wingren, Anette
    Immunohistochemical detection of tyrosine phosphatase SHP-1 predicts outcome after radical prostatectomy for localized prostate cancer2009In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 69, no 9 Supplement, p. LB-257-Article in journal (Other academic)
    Abstract [en]

    The protein tyrosine kinase (PTK) receptors and cytosolic signalling proteins as well as the protein tyrosine phosphatases (PTP) have important roles in regulation of growth and function of the benign and malignant prostate gland. Here we studied the expression levels and functions of the protein tyrosine phosphatase SHP-1 in prostate cancer cell lines and in benign and malignant human prostatic tissues. We found that SHP-1 is expressed at a high level in LNCaP prostate cancer cells compared to PC-3 cells. Silencing of SHP-1 expression with siRNA in LNCaP cells led to an increased rate of proliferation as measured by thymidine incorporation, whereas in PC3 cells in which SHP1 was overexpressed by transient transfection proliferation rate was decreased. We also examined SHP-1 expression in prostate cancer by immunohistochemical staining of tissue microarrays comprising tumor specimens from 122 prostate cancer patients. We found an inverse correlation between SHP-1 staining intensity and the time to biochemical recurrence as measured by a rise in the serum level of prostate-specific antigen (PSA) in prostate cancer patients. In conclusion, our results suggest that a low level of SHP-1 expression in prostate cancer cells is associated with high proliferation rate and with an increased risk of biochemical recurrence after radical prostatectomy for localized prostate cancer.

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