Expression of stathmin/op18 as a significant prognostic factor for cervical carcinoma patients.

PURPOSE

Stathmin (Oncoprotein18), a ubiquitous and highly conserved 19-kDa cytosolic phosphoprotein, has been reported to play a critical role in mitosis and possibly other cellular processes, which is associated with tumor carcinogenesis and development. The purpose of this study was to examine the involvement of stathmin in human cervical carcinogenesis and to evaluate its prognostic significance in human cervical carcinoma.

METHODS

Using semiquantitative RT-PCR and Western blotting, we detected the expression of stathmin in human normal cervical epithelial cell line, immortalized cervical epithelial cell lines, and cervical carcinoma cell lines. Additionally, we also detected the expression of stathmin protein in 15 cases of cervical carcinoma tissues and adjacent non-carcinomous margin tissues. Furthermore, specimens from 148 patients with different grade and stage cervical carcinoma were investigated by immunohistochemistry for stathmin expression. Correlations between the expression of stathmin and various clinicopathological factors were studied, while statistical analyses were performed to evaluate prognostic and diagnostic associations.

RESULTS

The levels of stathmin mRNA and protein expression were significantly higher in cervical carcinoma cells and immortalized cervical epithelial cells than in normal cervical epithelial cells (P < 0.05). Moreover, Western blotting revealed high stathmin protein expression in 73.3% (11/15) cervical carcinoma tissues, while stathmin were overexpressed in tumor tissues as compared with adjacent non-carcinomous margin samples (P = 0.017). In addition, immunohistochemical staining revealed stathmin immunoreactivity in 81.1% (120/148) of cervical carcinoma tissues and high stathmin expression was significantly correlated with clinical stage (P = 0.006), T classification (P = 0.012), regional lymph node metastasis (P = 0.005) and hematogenous metastasis (P = 0.021). Kaplan-Meier analysis showed that high stathmin positivity was significantly associated with a shorter survival time (P < 0.001). Clinical stage (P = 0.0022), T classification (P = 0.0035), regional lymph node (P = 0.0008) or hematogenous metastasis (P = 0.0015) were also associated with survival time. Furthermore, by Cox multivariate analysis, only lymph node (P = 0.0052) or hematogenous metastasis (P = 0.0046) maintained their significance as independent prognostic factors, although stathmin was not an independent prognostic factor (risk ratio: 1.45; P = 0.0624).

CONCLUSIONS

Stathmin expression correlates with cervical carcinogenesis and tumor progression. This molecule is a valuable prognostic marker in patients with cervical carcinoma.