Paradoxically Abundant Expression of Bcl-2 and Adrenomedullin in Invasive Cervical Squamous Carcinoma

Background: The purpose of this study was to identify the role of Bcl-2 protein and adrenomedullin (AM) expression in relation to apoptosis in the neoplastic changes of squamous epithelium of the uterine cervix.

Methods: Apoptosis in sections of normal cervical epithelium, cervical intraepithelial neoplasia (CIN), and invasive squamous cell carcinoma was determined by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling (TUNEL) assay. Bcl-2 protein and AM expression were analyzed using the avidin-biotin immunoperoxidase method.

Results: On the basis of the TUNEL assay, the apoptosis positive rate of the nuclei in early invasive squamous carcinoma and in bulky invasive squamous carcinoma was significantly higher than that in normal cervical epithelium, but no such increase in the apoptosis-positive rate was noted in the nuclei in CIN. Immunohistochemical staining revealed that Bcl-2 protein and AM were immunolocalized in the cytoplasm of invasive squamous carcinoma cells, but not in either CIN lesions or normal cervical epithelium. Bcl-2 protein expression was more prominent in bulky invasive squamous carcinoma cells than in early invasive squamous carcinoma cells. AM expression was also more abundant in bulky invasive squamous carcinoma compared with that in early invasive squamous carcinoma.

Conclusion: The present results suggest that the expression of Bcl-2 protein and AM in invasive squamous carcinoma may play crucial roles in selecting carcinoma cells resistant to apoptosis and in promoting malignant progression.