Annexin A5 protein expression is associated with the histological differentiation of uterine cervical squamous cell carcinoma in patients with an increased serum concentration.

Annexin A5 (ANXA5) is a calcium-dependent phospholipid-binding protein belonging to the annexin family and is expressed abnormally in several types of carcinoma. In the present study, ANXA5 protein expression was evaluated by western blot analysis in a series of 60 human uterine cervical squamous cell carcinomas (UCSCCs) to search for molecular alterations that may be able to serve as useful diagnostic/prognostic markers. The upregulation of ANXA5 expression was observed in 48/60 UCSCC cases (80%), whereas a weak expression was observed in the 25 normal uterine cervical tissues. ANXA5 expression was also analyzed by immunohistochemical staining, western blot and reverse transcription-polymerase chain reaction (RT-PCR) assays of the UCSCC and uterine cervical normal tissue lesions. All dysplastic tissues showed significantly increased ANXA5 expression compared with the weak signal observed in normal epithelia. A close association was observed between the ANXA5 expression levels and the histological grade of UCSCC. Compared with moderately and well-differentiated tumors, there was a significant increase in ANXA5 expression in poorly differentiated tumors. Furthermore, ANXA5 concentrations in the blood serum of the patients were significantly increased. Our findings clearly identify ANXA5 as an effective differentiation marker for the histopathological grading of UCSCCs and for the detection of epithelial dysplasia. The results from our study support the critical role of ANXA5 in the molecular profiling of UCSCC.