Prognostic value of EphA2 and EphrinA-1 in squamous cell cervical carcinoma

Gynecol Oncol. 2004 Aug;94(2):312-9. doi: 10.1016/j.ygyno.2004.05.019.


Objectives: To analyze the expressions of the protein and mRNA of EphA2 and EphrinA-1 in squamous cell cervical carcinomas and explore their prognostic value in cervical carcinoma.

Methods: Immunohistochemistry was used to assess the protein expressions of EphA2 and EphrinA-1 in 206 patients with squamous cervical carcinoma FIGO stage Ia-IVb. Frozen tissues from 20 cases in which the tumors showed variable EphA2 and EphrinA-1protein expressions were used for laser capture microdissection (LCM). About 50 cancer cells in each frozen section were captured with the LCM method and processed for RT-PCR detection of EphA2 and EphrinA-1 mRNA.

Results: Among the 206 squamous cervical carcinomas, 23 (11.2%) showed negative, 94(45.6%) weakly positive, 72 (35.0%) moderately positive, and 17 (8.3%) strongly positive for EphA2 immunostaining. For EphrinA-1 protein expression, 17 tumors (8.3%) showed negative, 95 (46.1%) weakly positive, 71(34.5%) moderately positive, and 23 (11.2%) strongly positive. EphA2 and EphrinA-1 often colocalized in the same tumor areas and vascular endothelial cells. Variable amount of mRNA expressions of EphA2 and EphrinA-1 were observed in the 20 tumors analyzed. There was no significant correlation between the overexpressions of EphA2/EphrinA-1 and age and FIGO stage. High level of EphA2 was significantly associated with overall survival in univariate and multivariate analysis. Moderate to high EphrinA-1 protein expression was significantly associated with overall survival in multivariate analysis. The combined high level of expression of EhpA2 and moderate to high level of expression of EphrinA-1 was a strong predictor of overall survival.

Conclusions: High levels of EphA2 together with moderate to high level of EphrinA-1 protein expressions in squamous cervical carcinoma were predictive for a shorter overall survival and these proteins may be valuable prognostic markers.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy
  • Endothelium, Vascular / metabolism
  • Ephrin-A1 / biosynthesis*
  • Ephrin-A1 / genetics
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptor, EphA2 / biosynthesis*
  • Receptor, EphA2 / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / therapy


  • Ephrin-A1
  • RNA, Messenger
  • Receptor, EphA2