Cyclins and Proliferation Markers in Early Squamous Cervical Carcinoma

Gynecol Oncol. 2004 Jan;92(1):40-6. doi: 10.1016/j.ygyno.2003.10.022.


Objectives: To examine the prognostic significance of the protein expression of cyclin E, cyclin A and cyclin D3, and of the proliferation markers Ki-67 and BM28 in early squamous cervical carcinoma (SCC).

Methods: Tissue blocks from 221 patients who underwent radical hysterectomy and bilateral lymphadenectomy at our institution for stage IB SCC between 1987 and 1993 were available for this study. Immunohistochemistry using monoclonal antibodies against cyclin E, cyclin A, cyclin D3, Ki-67 and BM28 was used to examine protein expression. Ten patients who underwent hysterectomy for uterine prolapse served as controls.

Results: Cyclin E, cyclin A, Ki-67 and BM28 expression was increased in SCC and high expression was observed in 81.5% (180/221), 35% (78/221), 25.5% (56/221) and 92% (204/221) of tumors, respectively. Cyclin D3 was decreased in SCC and low expression was found in 50.5% (111/220) of tumors. In univariate analysis, all classical clinicopathological parameters but none of the investigated proteins were associated with prognosis. In multivariate analysis, only deep stromal invasion was independently related to survival.

Conclusion: Cyclin E, cyclin A and cyclin D3 and the proliferation markers Ki-67 and BM28 are not independently associated with prognosis in stage IB SCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / biosynthesis*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Cycle Proteins / biosynthesis
  • Cyclins / biosynthesis*
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / biosynthesis
  • Middle Aged
  • Minichromosome Maintenance Complex Component 2
  • Nuclear Proteins / biosynthesis
  • Prognosis
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology


  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • Cyclins
  • Ki-67 Antigen
  • Nuclear Proteins
  • MCM2 protein, human
  • Minichromosome Maintenance Complex Component 2