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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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A Novel Biomarker for Staging Human Prostate Adenocarcinoma: Overexpression of Matriptase with Concomitant Loss of its Inhibitor, Hepatocyte Growth Factor Activator Inhibitor-1

Mohammad Saleem, Vaqar Mustafa Adhami, Weixiong Zhong, B. Jack Longley, Chen-Yong Lin, Robert B. Dickson, Shannon Reagan-Shaw, David F. Jarrard and Hasan Mukhtar
Mohammad Saleem
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Vaqar Mustafa Adhami
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Weixiong Zhong
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B. Jack Longley
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Chen-Yong Lin
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Robert B. Dickson
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Shannon Reagan-Shaw
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David F. Jarrard
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Hasan Mukhtar
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DOI: 10.1158/1055-9965.EPI-05-0737 Published February 2006
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  • Figure 1.
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    Figure 1.

    Expression of (A) matriptase and (B) HAI-1 protein in NHPE and prostate cancer cells LNCaP, CWR22Rν1, DU145, and PC-3 by Western blotting. Equal loading of protein was confirmed by stripping the blots and reprobing with β-actin antibody. The histogram indicates the relative density of the bands normalized to β-actin. Columns, mean of relative densities; bars, ± SE; NS, nonsignificant.

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    Figure 2.

    Expression of (A) matriptase and (B) HAI-1 mRNA in NHPE and prostate cancer cells LNCaP, CWR22Rν1, DU145, and PC-3 by RT-PCR. Equal loading of RT-PCR product was confirmed by GAPDH as an internal control. The histogram indicates the relative density of bands normalized to GAPDH. Columns, mean of relative densities; bars, ± SE; NS, nonsignificant.

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    Figure 3.

    Immunostaining for matriptase and HAI-1 in representative specimens of positive and negative controls. A negative control in which CaP tissues were incubated with normal mouse IgG replacing the anti-HIA-1 or matriptase monoclonal antibody (top). Positive controls for matriptase (middle) and HAI-1 (bottom) using the breast carcinoma specimens to show the specificity of the antibodies and quality of the immunohistochemical staining. The breast cancer specimens showed that both HAI-1 and matriptase were only present in the ductal and lobular epithelial cells, whereas the stroma was negative for both markers. Arrows, staining for matriptase and HAI-1 staining in the ductal and lobular epithelial cells. Original magnification, ×10; insets, ×40.

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    Figure 4.

    Box plots for matriptase (A) and HAI-1 (B) protein based on staining pattern in normal, BPH, PIN, and prostate cancer specimens of tumor grades 1 to 3. The intensity of staining was graded semiquantitatively by assigning a score to each tissue specimen. *, P < 0.05 compared with normal; black bar in gray box, median values.

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    Figure 5.

    Immunostaining for matriptase in representative specimens of (A) normal, BPH, PIN (B) CaP specimens of tumor grades 1 to 3, and (C) in specimens with adjacent normal and cancerous regions. CaP specimens were assigned tumor grades on the basis of Gleason pattern and Gleason score as described in Materials and Methods. Immunoreactive matriptase protein was observed in a coarsely granular pattern in cell cytoplasms of epithelial cells of BPH and of grade 1, grade 2 and grade 3 prostatic adenocarcinoma. There was minimal staining of occasional stromal cells. Matriptase expression was weak in normal and moderate to strong in BPH, PIN and advanced CaP specimens. Embedded Image, staining for matriptase in cancer regions; Embedded Image, staining for matriptase in normal regions. Original magnification, ×10; insets, ×40.

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    Figure 6.

    Immunostaining for HAI-1 protein in representative specimens of normal (A), BPH, PIN, CaP of Gleason patterns 2 to 4 (B), and in specimens with adjacent normal and cancerous regions (C). CaP specimens were assigned tumor grades on the basis of Gleason pattern and Gleason score as described in Materials and Methods. Staining for HAI-1 was positive in the cytoplasm of the stromal cells of normal and BPH but was progressively lost in CaP specimens. Embedded Image, cancerous region; Embedded Image, normal regions. HAI-1 protein expression was lost in both cancer as well as adjacent normal regions in CaP specimens of Gleason pattern 4. Original magnification, ×10; insets, ×40.

Tables

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  • Table 1.

    Expression of matriptase and HAI-1 in normal human prostate, BPH, PIN, and adenocarcinoma specimens

    Specimen typeMatriptase staining intensity
    HAI-1 staining intensity
    TotalNoneWeakModerateStrongPTotalNoneWeakModerateStrongP
    Total481162011401314121
    Normal651000.05*611400.05*
    BPH63030162770
    PIN403100.05*53200
    Carcinoma (all grades)323216110.0015*1374110.05*
    Grade 12002021100
    Grade 210205384211
    Grade 22012980.01*32100
    • NOTE: The expression of matriptase and HAI-1 was evaluated as staining of the tissue as none (0), weak (1), moderate (2), and strong (3). Fisher exact test was used to examine the association between staining intensity and tissue type or staining intensity and tumor grade (for tumor specimen only).

    • ↵* P < 0.05 was considered significant.

  • Table 2.

    Expression of matriptase and HAI-1 in pair-matched human prostate adenocarcinoma specimens

    Specimen TypeMatriptase staining intensity
    HAI-1 staining intensity
    TotalNoneWeakModerateStrongPTotalNoneWeakModerateStrongP
    Carcinoma (all grades)422120190.0001*421715910.05*
    Grade 14102141300
    Grade 214001310.001*140581
    Grade 324115170.001*2416710
    • NOTE: The expression of matriptase and HAI-1 was evaluated as staining of the tissue as none (0), weak (1), moderate (2), and strong (3). Fisher exact test was used to examine the association between staining intensity and tumor grade.

    • ↵* P < 0.05 was considered significant.

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Cancer Epidemiology Biomarkers & Prevention: 15 (2)
February 2006
Volume 15, Issue 2
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A Novel Biomarker for Staging Human Prostate Adenocarcinoma: Overexpression of Matriptase with Concomitant Loss of its Inhibitor, Hepatocyte Growth Factor Activator Inhibitor-1
Mohammad Saleem, Vaqar Mustafa Adhami, Weixiong Zhong, B. Jack Longley, Chen-Yong Lin, Robert B. Dickson, Shannon Reagan-Shaw, David F. Jarrard and Hasan Mukhtar
Cancer Epidemiol Biomarkers Prev February 1 2006 (15) (2) 217-227; DOI: 10.1158/1055-9965.EPI-05-0737

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A Novel Biomarker for Staging Human Prostate Adenocarcinoma: Overexpression of Matriptase with Concomitant Loss of its Inhibitor, Hepatocyte Growth Factor Activator Inhibitor-1
Mohammad Saleem, Vaqar Mustafa Adhami, Weixiong Zhong, B. Jack Longley, Chen-Yong Lin, Robert B. Dickson, Shannon Reagan-Shaw, David F. Jarrard and Hasan Mukhtar
Cancer Epidemiol Biomarkers Prev February 1 2006 (15) (2) 217-227; DOI: 10.1158/1055-9965.EPI-05-0737
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