Summary: | 碩士 === 國立臺灣大學 === 臨床牙醫學研究所 === 100 === Background
Of the NPM family (nucleophosmin family), NPM1 involves broad physiological functions in the human body, such as DNA replication, transcription and repair, cell cycle control, ribosome biogenesis, apoptosis, protein synthesis and centrosome replication. NPM1 is also known for its effect on tumor cell proliferation and metastasis. Recent cancer research has shown increasingly significant expression of NPM1 in many human cancers, including colon, bladder, and liver. Focused in this research are expression of NPM1 in pathological specimens of oral cancer patients, and the correlation between expression of NPM1 and clinical, pathological parameters, and survival time.
Materials and Methods
Examined in this study were 96 specimens diagnosed as oral squamous cell carcinoma (OSCC) and 45 specimens of oral epithelial dysplasia (OED). 29 cases of normal oral mucosa (NOM) were also observed for comparison. With a NPM1 monoclonal antibody, immunohistochemistry (IHC) stain was performed for detecting expression of NPM1 in these tissue sections. The degree of positive staining was recorded and graded as labeling index (LI). Finally, the correlations between expression of NPM1, clinical and pathologic parameters, and the overall survival of OSCC patients were analyzed statistically via chi-square test, Cox proportional hazard regression model, and Kaplan-Meier plots.
Results
The labeling index of NPM1 was significantly higher in OSCC specimens (p<0.001). The average LI of NPM1 in OSCC specimens was 58%. In OED specimens, the average LI was 29%. In NOM, the average LI was only 15%. Meanwhile, higher NPM1 LIs indicated larger tumor size (T3 and T4 status), nodal metastasis and later clinical stage (Stage 3 and stage 4). These results were all revealed with statistical significance (Chi-square test; p<0.05).
As Cox proportional hazard regression model, the tumor size (T status), nodal metastasis (N status), clinical stage, and the LIs of NPM1 were statistically significant. Multivariate analysis revealed that tumor size (T status), nodal metastasis (N status) and the LIs of NPM1 were independent factors of patient survival (p<0.05).
Kaplan-Meier survival analysis showed that patients had shorter survival time with advanced tumor sizes, nodal metastasis, later clinical staging, and high LIs of NPM1.
Conclusions
The expression of NPM1 was higher in OSCC specimen. The labeling index of NPM1 has strong correlation with several clinicopathological parameters and survival time. In OSCC patients, higher NPM1 expression seemed to indicate shorter overall survival. Judging from the above analysis, NPM1 is probably a potential prognostic factor of OSCC.
|