Molecular events associated with dysplastic morphologic transformation and initiation of ovarian tumorigenicity

Dong Hua Yang, Elizabeth R. Smith, Cynthia Cohen, Hong Wu, Christos Patriotis, Andrew K. Godwin, Thomas C. Hamilton, Xiangxi Xu

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

BACKGROUND. Disabled-2 (Dab2), a candidate tumor suppressor of ovarian carcinoma, frequently (around 80%) loses its expression in ovarian tumors. Expression of exogenous Dab2 in tumor cell lines negatively regulates growth and suppresses the downstream signal of the Ras/mitogen activated protein kinase mitogenic pathway. The inactivation of Dab2 is believed to be an early event in ovarian tumorigenicity. METHODS. The authors analyzed the correlation among expression of Dab2, presence of basement membrane (collagen IV and laminin), morphologic alteration of the surface epithelial cells, and expression of the mitotic index marker Mib-1 in 50 archived ovarian tumors by an immunohistochemical approach. The stainings of Dab2, Mib-1, collagen IV, and laminin in premalignant lesions bordering both normal and neoplastic ovarian surface epithelium from adjacent slides were analyzed in 50 ovarian tumors. RESULTS. In these 50 ovarian tumors, the percentage of Mib-1 positive tumor cells distributed in a wide range, from 1% to 75%, and there has no strong correlation with the expression of Dab2. However, in the premalignant regions bordering tumor and normal ovarian surface epithelium, the loss of Dab2 expression closely correlated with the dysplastic morphologic transition and Mib-1 expression of the ovarian surface epithelial cells. In 20 foci in 12 out of the 50 tumors, a transition from normal to neoplastic morphology within a contiguous epithelium was observed, and in all cases the morphologic change correlated with the loss of Dab2 staining. In addition, the collagen and laminin staining of the basement membrane were absent or weakened in pre-malignant epithelium prior to loss of Dab2 expression in all these 20 cases. Nevertheless, collagen IV and laminin were detectable in established adenomas on the same tumor slides. CONCLUSIONS. The loss of Dab2 is closely associated with the transition of ovarian surface epithelial cells to premalignant states and is likely involved in the initiation of ovarian tumorigenicity. Transient loss of collagen IV and laminin in the basement membrane of the premalignant epithelium and subsequent inactivation of Dab2 are common early events associated with tumorigenicity of the ovarian surface epithelium.

Original languageEnglish
Pages (from-to)2380-2392
Number of pages13
JournalCancer
Volume94
Issue number9
DOIs
StatePublished - May 1 2002
Externally publishedYes

Fingerprint

Laminin
Epithelium
Collagen
Neoplasms
Basement Membrane
Epithelial Cells
Staining and Labeling
Mitotic Index
Mitogen-Activated Protein Kinases
Tumor Cell Line
Adenoma
Carcinoma
Growth

Keywords

  • Basement membrane
  • Collagen IV
  • Disabled-2
  • Epithelium
  • Extracellular matrix
  • Ki67
  • Laminin
  • Mib-1
  • Ovarian carcinoma
  • Premalignant lesion

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Molecular events associated with dysplastic morphologic transformation and initiation of ovarian tumorigenicity. / Yang, Dong Hua; Smith, Elizabeth R.; Cohen, Cynthia; Wu, Hong; Patriotis, Christos; Godwin, Andrew K.; Hamilton, Thomas C.; Xu, Xiangxi.

In: Cancer, Vol. 94, No. 9, 01.05.2002, p. 2380-2392.

Research output: Contribution to journalArticle

Yang, DH, Smith, ER, Cohen, C, Wu, H, Patriotis, C, Godwin, AK, Hamilton, TC & Xu, X 2002, 'Molecular events associated with dysplastic morphologic transformation and initiation of ovarian tumorigenicity', Cancer, vol. 94, no. 9, pp. 2380-2392. https://doi.org/10.1002/cncr.10497
Yang, Dong Hua ; Smith, Elizabeth R. ; Cohen, Cynthia ; Wu, Hong ; Patriotis, Christos ; Godwin, Andrew K. ; Hamilton, Thomas C. ; Xu, Xiangxi. / Molecular events associated with dysplastic morphologic transformation and initiation of ovarian tumorigenicity. In: Cancer. 2002 ; Vol. 94, No. 9. pp. 2380-2392.
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title = "Molecular events associated with dysplastic morphologic transformation and initiation of ovarian tumorigenicity",
abstract = "BACKGROUND. Disabled-2 (Dab2), a candidate tumor suppressor of ovarian carcinoma, frequently (around 80{\%}) loses its expression in ovarian tumors. Expression of exogenous Dab2 in tumor cell lines negatively regulates growth and suppresses the downstream signal of the Ras/mitogen activated protein kinase mitogenic pathway. The inactivation of Dab2 is believed to be an early event in ovarian tumorigenicity. METHODS. The authors analyzed the correlation among expression of Dab2, presence of basement membrane (collagen IV and laminin), morphologic alteration of the surface epithelial cells, and expression of the mitotic index marker Mib-1 in 50 archived ovarian tumors by an immunohistochemical approach. The stainings of Dab2, Mib-1, collagen IV, and laminin in premalignant lesions bordering both normal and neoplastic ovarian surface epithelium from adjacent slides were analyzed in 50 ovarian tumors. RESULTS. In these 50 ovarian tumors, the percentage of Mib-1 positive tumor cells distributed in a wide range, from 1{\%} to 75{\%}, and there has no strong correlation with the expression of Dab2. However, in the premalignant regions bordering tumor and normal ovarian surface epithelium, the loss of Dab2 expression closely correlated with the dysplastic morphologic transition and Mib-1 expression of the ovarian surface epithelial cells. In 20 foci in 12 out of the 50 tumors, a transition from normal to neoplastic morphology within a contiguous epithelium was observed, and in all cases the morphologic change correlated with the loss of Dab2 staining. In addition, the collagen and laminin staining of the basement membrane were absent or weakened in pre-malignant epithelium prior to loss of Dab2 expression in all these 20 cases. Nevertheless, collagen IV and laminin were detectable in established adenomas on the same tumor slides. CONCLUSIONS. The loss of Dab2 is closely associated with the transition of ovarian surface epithelial cells to premalignant states and is likely involved in the initiation of ovarian tumorigenicity. Transient loss of collagen IV and laminin in the basement membrane of the premalignant epithelium and subsequent inactivation of Dab2 are common early events associated with tumorigenicity of the ovarian surface epithelium.",
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T1 - Molecular events associated with dysplastic morphologic transformation and initiation of ovarian tumorigenicity

AU - Yang, Dong Hua

AU - Smith, Elizabeth R.

AU - Cohen, Cynthia

AU - Wu, Hong

AU - Patriotis, Christos

AU - Godwin, Andrew K.

AU - Hamilton, Thomas C.

AU - Xu, Xiangxi

PY - 2002/5/1

Y1 - 2002/5/1

N2 - BACKGROUND. Disabled-2 (Dab2), a candidate tumor suppressor of ovarian carcinoma, frequently (around 80%) loses its expression in ovarian tumors. Expression of exogenous Dab2 in tumor cell lines negatively regulates growth and suppresses the downstream signal of the Ras/mitogen activated protein kinase mitogenic pathway. The inactivation of Dab2 is believed to be an early event in ovarian tumorigenicity. METHODS. The authors analyzed the correlation among expression of Dab2, presence of basement membrane (collagen IV and laminin), morphologic alteration of the surface epithelial cells, and expression of the mitotic index marker Mib-1 in 50 archived ovarian tumors by an immunohistochemical approach. The stainings of Dab2, Mib-1, collagen IV, and laminin in premalignant lesions bordering both normal and neoplastic ovarian surface epithelium from adjacent slides were analyzed in 50 ovarian tumors. RESULTS. In these 50 ovarian tumors, the percentage of Mib-1 positive tumor cells distributed in a wide range, from 1% to 75%, and there has no strong correlation with the expression of Dab2. However, in the premalignant regions bordering tumor and normal ovarian surface epithelium, the loss of Dab2 expression closely correlated with the dysplastic morphologic transition and Mib-1 expression of the ovarian surface epithelial cells. In 20 foci in 12 out of the 50 tumors, a transition from normal to neoplastic morphology within a contiguous epithelium was observed, and in all cases the morphologic change correlated with the loss of Dab2 staining. In addition, the collagen and laminin staining of the basement membrane were absent or weakened in pre-malignant epithelium prior to loss of Dab2 expression in all these 20 cases. Nevertheless, collagen IV and laminin were detectable in established adenomas on the same tumor slides. CONCLUSIONS. The loss of Dab2 is closely associated with the transition of ovarian surface epithelial cells to premalignant states and is likely involved in the initiation of ovarian tumorigenicity. Transient loss of collagen IV and laminin in the basement membrane of the premalignant epithelium and subsequent inactivation of Dab2 are common early events associated with tumorigenicity of the ovarian surface epithelium.

AB - BACKGROUND. Disabled-2 (Dab2), a candidate tumor suppressor of ovarian carcinoma, frequently (around 80%) loses its expression in ovarian tumors. Expression of exogenous Dab2 in tumor cell lines negatively regulates growth and suppresses the downstream signal of the Ras/mitogen activated protein kinase mitogenic pathway. The inactivation of Dab2 is believed to be an early event in ovarian tumorigenicity. METHODS. The authors analyzed the correlation among expression of Dab2, presence of basement membrane (collagen IV and laminin), morphologic alteration of the surface epithelial cells, and expression of the mitotic index marker Mib-1 in 50 archived ovarian tumors by an immunohistochemical approach. The stainings of Dab2, Mib-1, collagen IV, and laminin in premalignant lesions bordering both normal and neoplastic ovarian surface epithelium from adjacent slides were analyzed in 50 ovarian tumors. RESULTS. In these 50 ovarian tumors, the percentage of Mib-1 positive tumor cells distributed in a wide range, from 1% to 75%, and there has no strong correlation with the expression of Dab2. However, in the premalignant regions bordering tumor and normal ovarian surface epithelium, the loss of Dab2 expression closely correlated with the dysplastic morphologic transition and Mib-1 expression of the ovarian surface epithelial cells. In 20 foci in 12 out of the 50 tumors, a transition from normal to neoplastic morphology within a contiguous epithelium was observed, and in all cases the morphologic change correlated with the loss of Dab2 staining. In addition, the collagen and laminin staining of the basement membrane were absent or weakened in pre-malignant epithelium prior to loss of Dab2 expression in all these 20 cases. Nevertheless, collagen IV and laminin were detectable in established adenomas on the same tumor slides. CONCLUSIONS. The loss of Dab2 is closely associated with the transition of ovarian surface epithelial cells to premalignant states and is likely involved in the initiation of ovarian tumorigenicity. Transient loss of collagen IV and laminin in the basement membrane of the premalignant epithelium and subsequent inactivation of Dab2 are common early events associated with tumorigenicity of the ovarian surface epithelium.

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KW - Epithelium

KW - Extracellular matrix

KW - Ki67

KW - Laminin

KW - Mib-1

KW - Ovarian carcinoma

KW - Premalignant lesion

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