Altered expression of transforming growth factor-β1 in cervical neoplasia as an early biomarker in carcinogenesis of the uterine cervix

John T. Comerci, Carolyn D. Runowicz, Kathleen C. Flanders, Carol De Victoria, Abbie L. Fields, Anna S. Kadish, Gary L. Goldberg

Research output: Contribution to journalArticle

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Abstract

BACKGROUND. Transforming growth factor-β1 (TGF-β1) is a potent growth inhibitor of epithelial cell growth, but can also stimulate stromal cell growth. Loss of responsiveness to TGF-β1 or loss of TGF-β1 itself may be important in the progression of cervical intraepithelial neoplasia (CIN) to invasive cervical carcinoma. METHODS. To examine the expression of TGF-β in early stages of malignant transformation of the uterine cervix, paraffin embedded tissue samples from 11 patients with normal cervical epithelium, 15 with CIN I-III, 12 with microinvasive, and 18 with invasive squamous cell carcinoma were examined using an immunohistochemical technique. Tissues were immunostained with polyclonal antibodies that react with intracellular and extracellular forms of TGF-β1. RESULTS. Percent positive staining for the intracellular form of TGF-β1 was 100% for normal epithelium, 73.3% for CIN, and 44.1% for invasive carcinomas (P = 0.002). Percent positive staining for the extracellular form of TGF-β1 was 63.6% for stroma underlying normal epithelium, 60% for stroma associated with CIN, and 94.1% for stroma surrounding invasive cancer (P = 0.007). CONCLUSIONS. Decreased expression of intracellular TGF-β1 in neoplastic epithelium and increased expression of extracellular TGF-β1 in stroma associated with invasive cervical carcinoma suggest that an early event in the neoplastic transformation of cervical epithelial cells may involve the loss of TGF-β1. Tumor progression may be indirectly promoted by TGF-β1 secreted into or produced by supporting stromal elements.

Original languageEnglish (US)
Pages (from-to)1107-1114
Number of pages8
JournalCancer
Volume77
Issue number6
DOIs
StatePublished - Mar 15 1996

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Transforming Growth Factors
Cervix Uteri
Carcinogenesis
Biomarkers
Cervical Intraepithelial Neoplasia
Neoplasms
Epithelium
Carcinoma
Epithelial Cells
Staining and Labeling
Growth Inhibitors
Stromal Cells
Growth
Paraffin
Squamous Cell Carcinoma
Antibodies

Keywords

  • cervical cancer
  • cervical dysplasia
  • neoplastic transformation
  • transforming growth factor-β1

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Altered expression of transforming growth factor-β1 in cervical neoplasia as an early biomarker in carcinogenesis of the uterine cervix. / Comerci, John T.; Runowicz, Carolyn D.; Flanders, Kathleen C.; De Victoria, Carol; Fields, Abbie L.; Kadish, Anna S.; Goldberg, Gary L.

In: Cancer, Vol. 77, No. 6, 15.03.1996, p. 1107-1114.

Research output: Contribution to journalArticle

Comerci, John T. ; Runowicz, Carolyn D. ; Flanders, Kathleen C. ; De Victoria, Carol ; Fields, Abbie L. ; Kadish, Anna S. ; Goldberg, Gary L. / Altered expression of transforming growth factor-β1 in cervical neoplasia as an early biomarker in carcinogenesis of the uterine cervix. In: Cancer. 1996 ; Vol. 77, No. 6. pp. 1107-1114.
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abstract = "BACKGROUND. Transforming growth factor-β1 (TGF-β1) is a potent growth inhibitor of epithelial cell growth, but can also stimulate stromal cell growth. Loss of responsiveness to TGF-β1 or loss of TGF-β1 itself may be important in the progression of cervical intraepithelial neoplasia (CIN) to invasive cervical carcinoma. METHODS. To examine the expression of TGF-β in early stages of malignant transformation of the uterine cervix, paraffin embedded tissue samples from 11 patients with normal cervical epithelium, 15 with CIN I-III, 12 with microinvasive, and 18 with invasive squamous cell carcinoma were examined using an immunohistochemical technique. Tissues were immunostained with polyclonal antibodies that react with intracellular and extracellular forms of TGF-β1. RESULTS. Percent positive staining for the intracellular form of TGF-β1 was 100{\%} for normal epithelium, 73.3{\%} for CIN, and 44.1{\%} for invasive carcinomas (P = 0.002). Percent positive staining for the extracellular form of TGF-β1 was 63.6{\%} for stroma underlying normal epithelium, 60{\%} for stroma associated with CIN, and 94.1{\%} for stroma surrounding invasive cancer (P = 0.007). CONCLUSIONS. Decreased expression of intracellular TGF-β1 in neoplastic epithelium and increased expression of extracellular TGF-β1 in stroma associated with invasive cervical carcinoma suggest that an early event in the neoplastic transformation of cervical epithelial cells may involve the loss of TGF-β1. Tumor progression may be indirectly promoted by TGF-β1 secreted into or produced by supporting stromal elements.",
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AU - Runowicz, Carolyn D.

AU - Flanders, Kathleen C.

AU - De Victoria, Carol

AU - Fields, Abbie L.

AU - Kadish, Anna S.

AU - Goldberg, Gary L.

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N2 - BACKGROUND. Transforming growth factor-β1 (TGF-β1) is a potent growth inhibitor of epithelial cell growth, but can also stimulate stromal cell growth. Loss of responsiveness to TGF-β1 or loss of TGF-β1 itself may be important in the progression of cervical intraepithelial neoplasia (CIN) to invasive cervical carcinoma. METHODS. To examine the expression of TGF-β in early stages of malignant transformation of the uterine cervix, paraffin embedded tissue samples from 11 patients with normal cervical epithelium, 15 with CIN I-III, 12 with microinvasive, and 18 with invasive squamous cell carcinoma were examined using an immunohistochemical technique. Tissues were immunostained with polyclonal antibodies that react with intracellular and extracellular forms of TGF-β1. RESULTS. Percent positive staining for the intracellular form of TGF-β1 was 100% for normal epithelium, 73.3% for CIN, and 44.1% for invasive carcinomas (P = 0.002). Percent positive staining for the extracellular form of TGF-β1 was 63.6% for stroma underlying normal epithelium, 60% for stroma associated with CIN, and 94.1% for stroma surrounding invasive cancer (P = 0.007). CONCLUSIONS. Decreased expression of intracellular TGF-β1 in neoplastic epithelium and increased expression of extracellular TGF-β1 in stroma associated with invasive cervical carcinoma suggest that an early event in the neoplastic transformation of cervical epithelial cells may involve the loss of TGF-β1. Tumor progression may be indirectly promoted by TGF-β1 secreted into or produced by supporting stromal elements.

AB - BACKGROUND. Transforming growth factor-β1 (TGF-β1) is a potent growth inhibitor of epithelial cell growth, but can also stimulate stromal cell growth. Loss of responsiveness to TGF-β1 or loss of TGF-β1 itself may be important in the progression of cervical intraepithelial neoplasia (CIN) to invasive cervical carcinoma. METHODS. To examine the expression of TGF-β in early stages of malignant transformation of the uterine cervix, paraffin embedded tissue samples from 11 patients with normal cervical epithelium, 15 with CIN I-III, 12 with microinvasive, and 18 with invasive squamous cell carcinoma were examined using an immunohistochemical technique. Tissues were immunostained with polyclonal antibodies that react with intracellular and extracellular forms of TGF-β1. RESULTS. Percent positive staining for the intracellular form of TGF-β1 was 100% for normal epithelium, 73.3% for CIN, and 44.1% for invasive carcinomas (P = 0.002). Percent positive staining for the extracellular form of TGF-β1 was 63.6% for stroma underlying normal epithelium, 60% for stroma associated with CIN, and 94.1% for stroma surrounding invasive cancer (P = 0.007). CONCLUSIONS. Decreased expression of intracellular TGF-β1 in neoplastic epithelium and increased expression of extracellular TGF-β1 in stroma associated with invasive cervical carcinoma suggest that an early event in the neoplastic transformation of cervical epithelial cells may involve the loss of TGF-β1. Tumor progression may be indirectly promoted by TGF-β1 secreted into or produced by supporting stromal elements.

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