Expression and localization of maspin in cervical cancer and its role in tumor progression and lymphangiogenesis

OBJECTIVES: Cervical cancer is the most common malignant tumor in female reproductive tract and primarily metastasizes through the lymphatic system that will affect prognosis of patients. Maspin, a member of the serine protease inhibitors (serpins) super family, has recently been indicated as a tumor suppressor in many cancers. In this study, we investigated the clinical significance of maspin expression, especially the subcellular location of maspin and its functional role in progression and lymphangiogenesis, in cervical squamous cell carcinoma. METHODS: Labelled streptavidin biotin method (LSAB) was used to determine cytoplasmic and nuclear maspin expressions, respectively, in 13 cases of normal cervix, 15 cases of cervical intraepithelial neoplasia grade 3 (CIN3), 62 cases of squamous cell carcinoma (SCC) of the uterine cervix, and 13 cases of pelvic lymphatic nodes which were all positive lymphatic nodes in our selected cancer cases. LSAB is also used to detect podoplanin which is used for counting density of lymphatic microvessels (LMVD). The clinical significance of subcellular maspin expression and the relationship between maspin expression and LMVD in cervical cancer are analyzed. RESULTS: Both cytoplasmic and nuclear maspin expressions in SCC were significantly weaker than those of normal cervix and CIN3. Nuclear maspin expression showed a peak in CIN3 and then dropped in SCC. Declined maspin expression was correlated with later clinical stage, increased LMVD, and lymphatic metastasis. CONCLUSIONS: Our results suggest that subcellular location of maspin expression is a potential predictive factor in tumor progression and in patients’ prognosis of cervical cancer, and maspin plays a suppression role in lymphangiogenesis and metastasis.