Abnormal expression of sex steroid receptors and cell cycle-related molecules in adenocarcinoma in situ of the uterine cervix

Int J Gynecol Pathol. 1999 Apr;18(2):109-14.


It was recently reported that cervical adenocarcinoma showed an abnormal expression of estrogen receptor (ER) and cell cycle-related molecules (cyclin E, p53, p16, p21, and p27). To investigate whether similar alterations exist in glandular intraepithelial lesions, the expression of ER, progesterone receptor (PR), Ki-67, and the above cell cycle-related molecules was examined in 15 cases of glandular dysplasia (GD) and 10 cases of adenocarcinoma in situ (AIS), using the immunohistochemical technique. An expression of ER and PR was often decreased or missing in GD and, especially, in AIS. The Ki-67 labeling index was significantly higher in AIS than in GD or normal glandular cells. In GD, expression of all the cell cycle-related molecules was not recognized (except for a few p27-positive cases), a situation comparable to normal glands. In contrast, an abnormal expression of all the cell cycle-related molecules examined was demonstrated in AIS. There was a significant positive correlation, in terms of the extent of staining, between cyclin E and p21 in AIS. These results suggest that an altered expression of these molecules occurs in AIS as it does in invasive adenocarcinoma, and provide additional evidence supporting AIS as a precursor of cervical adenocarcinoma.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adult
  • Aged
  • Carcinoma in Situ / metabolism*
  • Cell Cycle Proteins / biosynthesis*
  • Cyclin E / biosynthesis
  • Cyclin-Dependent Kinase Inhibitor p16 / biosynthesis
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclins / biosynthesis
  • Enzyme Inhibitors / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / biosynthesis
  • Microtubule-Associated Proteins / biosynthesis
  • Middle Aged
  • Mitotic Index
  • Receptors, Estrogen / biosynthesis
  • Receptors, Progesterone / biosynthesis
  • Receptors, Steroid / biosynthesis*
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Proteins*
  • Uterine Cervical Dysplasia / metabolism*
  • Uterine Cervical Neoplasms / metabolism*


  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin E
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Enzyme Inhibitors
  • Ki-67 Antigen
  • Microtubule-Associated Proteins
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptors, Steroid
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27