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Imaging, Diagnosis, Prognosis

Cytoplasmic CD24 Expression in Colorectal Cancer Independently Correlates with Shortened Patient Survival

Wilko Weichert, Carsten Denkert, Mick Burkhardt, Tserenchunt Gansukh, Joachim Bellach, Peter Altevogt, Manfred Dietel and Glen Kristiansen
Wilko Weichert
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Carsten Denkert
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Mick Burkhardt
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Tserenchunt Gansukh
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Joachim Bellach
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Peter Altevogt
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Manfred Dietel
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Glen Kristiansen
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DOI: 10.1158/1078-0432.CCR-05-0606 Published September 2005
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  • Fig. 1.
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    Fig. 1.

    CD24 immunofluorescence. A, CD24 expression is virtually absent in the colon cancer cell line CX-2. Note strong exclusively membranous expression in the ovarian carcinoma cell line OVCAR-3, which served as positive control (inset). B, strong cytoplasmic and focal membranous expression of CD24 in the HT29 colon cancer cell line.

  • Fig. 2.
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    Fig. 2.

    CD24 immunohistochemistry. A, transition of low-grade dysplastic colonic epithelium in colon carcinoma. Note abrupt onset of predominantly membranous expression of CD24. B, interface between colon mucosa and colon carcinoma. Note strong predominantly cytoplasmic overexpression of CD24 in the neoplastic glands of this case. C, colon cancer with minimal focal membranous expression of CD24 (arrows). D, colon cancer with strong membranous expression of CD24 without cytoplasmic positivity. E, neoplastic colonic glands with strong cytoplasmic CD24 expression. F, liver metastasis of a colon carcinoma from the study cohort. Note strong simultaneous cytoplasmic and membranous expression of CD24.

  • Fig. 3.
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    Fig. 3.

    Patient survival in dependence of CD24 expression pattern. A and B, Kaplan-Meier survival curves for patients grouped for cytoplasmic CD24 expression (A, whole study cohort; B, patients without distant metastasis). Note dramatically reduced survival time for those patients whose tumors showed strong cytoplasmic positivity. C, survival curves for patients grouped for membranous CD24 expression.

Tables

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  • Table 1.

    Clinicopathologic characteristics of the colon cancer cohort

    Characteristicn (%)
    All cases147 (100)
    Age
        ≤65 y72 (49)
        >65 y75 (51)
    Dukes stage
        A33 (22.4)
        B54 (36.7)
        C48 (32.7)
        D12 (8.2)
    Tumor stage
        pT19 (6.1)
        pT234 (23.1)
        pT394 (63.9)
        pT410 (6.9)
    Nodal status
        pN088 (59.9)
        pN129 (19.7)
        pN230 (20.4)
    Distant metastasis
        Mx135 (91.8)
        pM112 (8.2)
    Grade
        16 (4.1)
        2117 (79.6)
        324 (16.3)
    Localization
        Left colon60 (40.8)
        Transversal colon21 (14.3)
        Right colon44 (29.9)
        Rectum22 (15)
  • Table 2.

    Associations between membranous CD24 expression and clinicopathologic variables

    CharacteristicmCD24 negativemCD24 weakmCD24 moderatemCD24 strongP
    All cases
    46 (31.3%)33 (22.4%)43 (29.3%)25 (17%)
    Age
        ≤65 y26 (36.1%)16 (22.2%)17 (23.6%)13 (18.1%)0.342*
        >65 y20 (26.7%)17 (22.7%)26 (34.6%)12 (16%)
    Dukes stage
        A9 (27.3%)9 (27.3%)9 (27.3%)6 (18.1%)0.412†
        B18 (33.3%)15 (27.8%)13 (24.1%)8 (14.8%)
        C17 (35.4%)9 (18.8%)17 (35.4%)5 (10.4%)
        D2 (16.7%)0 (0%)4 (33.3%)6 (50%)
    Tumor stage
        pT12 (22.2%)1 (11.1%)4 (44.5%)2 (22.2%)0.677†
        pT211 (32.4%)9 (26.5%)9 (26.5%)5 (14.6%)
        pT329 (30.9%)21 (22.3%)27 (28.7%)17 (18.1%)
        pT44 (40%)2 (20%)3 (30%)1 (10%)
    Nodal status
        pN027 (30.7%)24 (27.3%)24 (27.3%)13 (14.7%)0.400†
        pN110 (34.5%)4 (13.8%)10 (34.5%)5 (17.2%)
        pN29 (30%)5 (16.7%)9 (30%)7 (23.3%)
    Distant metastasis
        Mx44 (32.6%)33 (24.4%)39 (28.9%)19 (14.1%)0.006*
        pM12 (16.7%)0 (0%)4 (33.3%)6 (50%)
    Grade
        11 (16.7%)2 (33.3%)0 (0%)3 (50%)0.317†
        239 (33.3%)28 (23.9%)35 (29.9%)15 (12.9%)
        36 (25%)3 (12.5%)8 (33.3%)7 (29.2%)
    Localization
        Left colon24 (40%)14 (23.3%)12 (20%)10 (16.7%)0.013‡
        Transversal colon5 (23.8%)3 (14.3%)13 (61.9%)0 (0%)
        Right colon10 (22.7%)13 (29.6%)10 (22.7%)11 (25%)
        Rectum7 (31.8%)3 (13.6%)8 (36.4%)4 (18.2%)
    • Abbreviation: mCD24, membranous CD24 expression.

    • ↵* Fisher's exact test.

    • ↵† χ2 test for trends.

    • ↵‡ χ2 test.

  • Table 3.

    Associations between cytoplasmic CD24 expression and clinicopathologic variables

    CharacteristiccCD24 negativecCD24 weakcCD24 moderatecCD24 strongP
    All cases
    23 (15.6%)57 (38.8%)52 (35.4%)15 (10.2%)
    Age
        ≤65 y15 (20.8%)28 (38.9%)23 (31.9%)6 (8.4%)0.099*
        >65 y8 (10.6%)29 (38.7%)29 (38.7%)9 (12.0%)
    Dukes stage
        A10 (30.3%)12 (36.4%)10 (30.3%)1 (3%)0.002†
        B5 (9.3%)27 (50%)18 (33.3%)4 (7.4%)
        C7 (14.6%)17 (35.4%)18 (37.5%)6 (12.5%)
        D1 (8.3%)1 (8.3%)6 (50%)4 (33.4%)
    Tumor stage
        pT12 (22.2%)4 (44.5%)3 (33.3%)0 (0%)0.045†
        pT29 (26.5%)12 (35.3%)12 (35.3%)1 (2.9%)
        pT310 (10.6%)38 (40.4%)34 (36.2%)12 (12.8%)
        pT42 (20%)3 (30%)3 (30%)2 (20%)
    Nodal status
        pN015 (17%)38 (43.2%)29 (33%)6 (6.8%)0.038†
        pN14 (13.8%)11 (37.9%)13 (44.9%)1 (3.4%)
        pN24 (13.3%)8 (26.7%)10 (33.3%)8 (26.7%)
    Distant metastasis
        Mx22 (16.3%)56 (41.5%)46 (34.1%)11 (8.1%)0.005*
        pM11 (8.3%)1 (8.3%)6 (50%)4 (33.4%)
    Grade
        12 (33.3%)1 (16.7%)3 (50%)0 (0%)0.007†
        219 (16.2%)49 (41.9%)43 (36.8%)6 (5.1%)
        32 (8.3%)7 (29.2%)6 (25%)9 (37.5%)
    Localization
        Left colon13 (21.7%)19 (31.7%)20 (33.3%)8 (13.3%)0.374‡
        Transversal colon1 (4.8%)10 (47.5%)9 (42.9%)1 (4.8%)
        Right colon4 (9.1%)21 (47.7%)16 (36.4%)3 (6.8%)
        Rectum5 (22.8%)7 (31.8%)7 (31.8%)3 (13.6%)
    • Abbreviation: cCD24, cytoplasmic CD24 expression.

    • ↵* Fisher's exact test.

    • ↵† χ2 test for trends.

    • ↵‡ χ2 test.

  • Table 4.

    Univariate survival analysis of CD24 expression and clinicopathologic variables

    CasesEventsMean survival (mo)SEP*
    Age
        ≤65 y721475.03.60.0365
        >65 y752758.63.6
    Dukes stage
        A33469.83.4<0.0001
        B54583.82.7
        C482249.44.2
        D121019.16.0
    Tumor stage
        pT190Not reached—0.0008
        pT234775.94.9
        pT3942763.43.1
        pT410729.17.2
    Nodal status
        pN0881181.72.4<0.0001
        pN1291055.55.3
        pN2302028.74.0
    Distant metastasis
        Mx1353173.62.6<0.0001
        pM1121019.16.0
    Grade
        160Not reached—0.0007
        21172872.92.9
        3241342.56.6
    Localization
        Left602163.84.70.0861
        Transversal21661.46.8
        Right441361.13.9
        Rectum22178.11.9
    cCD24
        Negative23568.35.70.0018
        Weak571373.94.0
        Moderate521461.73.7
        Strong15931.57.0
    mCD24
        Negative461467.45.10.5244
        Weak33667.83.5
        Moderate431360.14.7
        Strong25858.55.7
    • ↵* Log-rank test.

  • Table. 5.

    Cox regression analysis of cases without distant metastasis (n = 135)

    Overall survival
    Relative risk95% confidence intervalP
    Age
        Per year1.0451.010-1.0820.010
    Tumor stage
        pT1/pT21.000
        pT3/pT41.2160.473-3.1300.685
    Lymph node status
        Per positive node1.1661.070-1.270<0.001
    Grade
        1/21.000
        32.2590.937-5.4460.070
    cCD24 expression
        Negative-moderate1.000
        Strong3.7071.338-10.2720.012
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Clinical Cancer Research: 11 (18)
September 2005
Volume 11, Issue 18
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Cytoplasmic CD24 Expression in Colorectal Cancer Independently Correlates with Shortened Patient Survival
Wilko Weichert, Carsten Denkert, Mick Burkhardt, Tserenchunt Gansukh, Joachim Bellach, Peter Altevogt, Manfred Dietel and Glen Kristiansen
Clin Cancer Res September 15 2005 (11) (18) 6574-6581; DOI: 10.1158/1078-0432.CCR-05-0606

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Cytoplasmic CD24 Expression in Colorectal Cancer Independently Correlates with Shortened Patient Survival
Wilko Weichert, Carsten Denkert, Mick Burkhardt, Tserenchunt Gansukh, Joachim Bellach, Peter Altevogt, Manfred Dietel and Glen Kristiansen
Clin Cancer Res September 15 2005 (11) (18) 6574-6581; DOI: 10.1158/1078-0432.CCR-05-0606
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