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PEA3 Is the Second Ets Family Transcription Factor Involved in Tumor Progression in Ovarian Carcinoma

Ben Davidson, Iris Goldberg, Walter H. Gotlieb, Juri Kopolovic, Gilad Ben-Baruch and Reuven Reich
Ben Davidson
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Iris Goldberg
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Walter H. Gotlieb
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Juri Kopolovic
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Gilad Ben-Baruch
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Reuven Reich
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DOI:  Published April 2003
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  • Fig. 1.
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    Fig. 1.

    PEA3 mRNA expression in advanced-stage ovarian carcinoma. A, d(T) control for mRNA integrity in a primary ovarian serous carcinoma. All cells are labeled (nitroblue tetrazolium-5-bromo-4-chloro-3-indolyl phosphate staining). B, an intestinal metastasis hybridized with a sense probe showing no labeling. Cells are counterstained with nuclear fast red. C shows weak, diffuse PEA3 expression in both the tumor and stromal cell compartments in a peritoneal metastasis from a short-term survivor diagnosed with FIGO stage IIIc serous carcinoma. D, diffuse intense expression (dark blue) of PEA3 mRNA in stromal cells of an omental metastasis in a FIGO stage IV serous carcinoma of a short-term survivor. Weak staining of tumor cells is also seen. E and F demonstrate coexpression of PEA3 and β1 integrin subunit mRNA in an omental metastasis from a long-term survivor. Both tumor and stromal cells are positive. G and H demonstrate coexpression of bFGF and EMMPRIN in the tumor shown in C. Stromal and tumor cells are labeled.

  • Fig. 2.
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    Fig. 2.

    Kaplan-Meier survival curves showing the correlation between PEA3 mRNA expression and disease outcome. A, the association between intense stromal cell PEA3 expression and disease-free survival. Patients with intensely labeled specimens (n = 14; solid line) had a mean disease-free survival of 14 months compared with 101 months for patients with weakly expressing or negative tumors (n = 47; dashed line; P = 0.019). Segregation of cases according to the three-tier system presented in “Results” showed comparable results (P = 0.048; data not shown). B, the association between intense stromal cell PEA3 expression and overall survival. Patients with intensely labeled specimens (n = 14; solid line) had a mean overall survival of 37 months, compared with 112 months for patients with weakly expressing or negative tumors (n = 47; dashed line; P = 0.029). C, the association between intense PEA3 expression in tumor cells and overall survival. Intense, weak, and negative expression (solid, long-dashed, and short-dashed lines, respectively) was associated with mean overall survival of 21, 108, and 76 months, respectively (P = 0.049).

Tables

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  • Table 1

    Tissue distribution of primary tumors and metastatic lesions according to tumor type

    Tumor typeNo. of patientsOvaryOmentumPeritoneumIntestineLNaOtherTotal no. of biopsies
    Serous28249633247
    Endometrioid33200005
    Mucinous22001003
    Undifferentiated11010002
    Clear cell11100013
    Neuroendocrine11000001
    Total363212743361
    • a LN, lymph node.

  • Table 2

    Survival data for long-term and short-term survivors

    Patient groupMean disease-free survival (mo)Mean overall survival (mo)DODaAWDNED
    Long-term survivors (n = 16)1191372311
    Short-term survivors (n = 20)4222000
    • a DOD, dead of disease; AWD, alive with disease; NED, no evidence of disease.

  • Table 3

    The distribution of PEA3 mRNA expression in tumors of long-term (n = 27) and short-term (n = 34) survivorsa

    A. Intensity
    CompartmentAbsentWeak/moderateIntense
    Long-term survivors
      Tumor cells2 (7%)25 (93%)0 (0%)
      Stromal cells5 (19%)20 (74%)2 (7%)
    Short-term survivors
      Tumor cells3 (9%)26 (76%)5 (15%)
      Stromal cells2 (6%)20 (59%)12 (35%)
    B. Extent
    Compartment0%1–20%21–100%
    Long-term survivors
      Tumor cells2 (7%)5 (19%)20 (74%)
      Stromal cells5 (19%)3 (11%)19 (70%)
    Short-term survivors
      Tumor cells3 (9%)6 (18%)25 (73%)
      Stromal cells2 (6%)6 (18%)26 (76%)
    • a P = 0.021 for intensity in stromal cells.

  • Table 4

    The association between labeling intensity for PEA3 mRNA in stromal cells and histological grade

    GradePEA3Total
    AbsentWeakIntense
    I19010P = 0.04
    II0246
    III6291045
    Total7401461
  • Table 5

    The association between labeling intensity for PEA3 in stromal cells and MMP-2 mRNA in carcinoma cells (56 specimens)

    MMP-2PEA3Total
    AbsentWeakIntense
    Absent451221P = 0.022
    Weak052025
    Intense11810
    Total5114056
  • Table 6

    The association between labeling intensity for PEA3 and β1 integrin subunit mRNA in carcinoma cells (50 specimens)

    β1 integrinPEA3Total
    AbsentWeakIntense
    Absent227029P = 0.039
    Weak011415
    Intense1416
    Total342550
  • Table 7

    The association between labeling intensity for PEA3 in carcinoma cells and labeling intensity for bFGF (61 specimens) and β1 integrin subunit (50 specimens) mRNA in stromal cells

    PEA3 (tumor cells)Total
    AbsentWeakIntense
    bFGF (stromal cells)
     Absent010010P = 0.036
     Weak417021
     Intense124530
     Total551561
    β1 integrin (stromal cells)
     Absent231134P = 0.012
     Weak09413
     Intense1203
     Total342550
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Clinical Cancer Research: 9 (4)
April 2003
Volume 9, Issue 4
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PEA3 Is the Second Ets Family Transcription Factor Involved in Tumor Progression in Ovarian Carcinoma
Ben Davidson, Iris Goldberg, Walter H. Gotlieb, Juri Kopolovic, Gilad Ben-Baruch and Reuven Reich
Clin Cancer Res April 1 2003 (9) (4) 1412-1419;

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PEA3 Is the Second Ets Family Transcription Factor Involved in Tumor Progression in Ovarian Carcinoma
Ben Davidson, Iris Goldberg, Walter H. Gotlieb, Juri Kopolovic, Gilad Ben-Baruch and Reuven Reich
Clin Cancer Res April 1 2003 (9) (4) 1412-1419;
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