The role of p-STAT3 (ser727) revealed by its association with Ki-67 in cervical intraepithelial neoplasia

Gynecol Oncol. 2005 Sep;98(3):446-52. doi: 10.1016/j.ygyno.2005.05.032.

Abstract

Objectives: Constitutive activation of signal transducer and activator of transcription 3 (STAT3) has been described in many types of cancers. However, the role of phospho-STAT3 (p-STAT3) at serine residue 727 is in large part undetermined. Our purposes of this study were to evaluate the expression patterns of p-STAT3 (ser727) in cervical intraepithelial neoplasia (CIN) and to explore its possible role in the progression of cervical cancer.

Methods: Paraffin-embedded sections from 56 patients including 20 CIN 1, 10 CIN 2, and 26 CIN 3 were collected in this study. Immunohistochemical analysis was performed, and the expression patterns of p-STAT3 (ser727) were categorized by semiquantitative method and further correlated with the CIN histopathologic grade using the chi(2) test with Bonferroni adjustment for multiple comparisons and with the proliferation marker Ki-67 expression using Fisher's Exact Test.

Results: The categorized high p-STAT3 (ser727) expression group in nuclei of dysplastic cells was significantly higher in CIN 3 (76.92%), in comparison with CIN 1/2 (13.33%, P < 0.001). Moreover, both the nuclear and cytoplasmic p-STAT3 (ser727) expressions were correlated with Ki-67 nuclear staining (P < 0.001 and < 0.001, respectively).

Conclusions: Our result revealed that aberrant expression levels of p-STAT3 (ser727) were significantly correlated with CIN lesion grade and cell proliferation. Evaluation of p-STAT3 (ser727) expression may provide additional prognostic information for the clinical course of the disease and therefore to be developed as a prognostic indicator for cervical cancer.

MeSH terms

  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / metabolism
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / metabolism*
  • Disease Progression
  • Female
  • Humans
  • Ki-67 Antigen / biosynthesis*
  • Ki-67 Antigen / metabolism
  • Phosphoproteins / biosynthesis*
  • Phosphoproteins / metabolism
  • Prognosis
  • STAT3 Transcription Factor
  • Serine / metabolism
  • Trans-Activators / biosynthesis
  • Trans-Activators / metabolism*
  • Uterine Cervical Dysplasia / metabolism*
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Ki-67 Antigen
  • Phosphoproteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Trans-Activators
  • Serine