Prognostic value of EphA2 and EphrinA-1 in squamous cell cervical carcinoma.
OBJECTIVE
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.
Department of Pathology, The Norwegian Radium Hospital, University of Oslo, Oslo 0310, Norway.
Dan
D
Wu
Zhenhe
Z
Suo
Gunnar B
GB
Kristensen
Shanshan
S
Li
Gunhild
G
Troen
Ruth
R
Holm
Jahn M
JM
Nesland
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D004730:Endothelium, Vascular / Q000378:metabolism; D036382:Ephrin-A1 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D036104:Receptor, EphA2 / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy
D036382:Ephrin-A1; D012333:RNA, Messenger; D036104:Receptor, EphA2