| Summary: | 碩士 === 國立臺灣大學 === 預防醫學研究所 === 96 === Purpose:
The aim of this study is to explore the expression of two molecular markers (p53 & PTTG1) in oral cancer tumorgenesis and to explore their association with the prognosis of patients with oral precancerous lesion and oral cancer.
Methods:
One hundred and forty one cases of formalin-fixed, paraffin-embedded specimens were collected and classified as patients group, including primary oral precancerous lesions (n=82) and squamous cell carinomas without distant metastasis (n=43). These patients received operation at the Department of Otolaryngology or Oral and Maxillofacial Surgery in NTUH during 1995-2001. On the other hand, sixteen specimens of normal oral mucosa were obtained during extraction of impacted permanent mandibular tooth in 2005 and classified as non-patients group. The expression of two biomarkers, p53 and PTTG1 in epithelial cells and cancer cells was measured with immunohistochemical staining and scored as labeling indices (LI). Patients’ clinicopathological parameters were retrieved from hospital records, including habits of alcohol smoking, betel nut chewing and cigarette smoking and the record of malignant development in precancerous lesions, cancer recurrence till May 2008. Mortality data was obtained from national death registry database. The expression of p53 and PTTG1 LI in normal oral mucosa, precancerous lesions and cancer were compared and adjusted with age, gender and lifestyle in linear regression. We analyzed the relation of initial p53 and PTTG1 LI with cancer development in precancerous lesions and recurrence or survival in oral cancers. The significance of p53 and PTTG1 LI in precancerous lesion with subsequent cancer development was determined in receiver operating characteristic (ROC) curve method. The point at which (sensitivity + specificity ) is maximized on the curve is taken as the best cut-off point and classified into two groups. Cox regression and time to event analysis with Kaplan-Meier curves method were used to compare the hazard ratio and determine the significant difference of these two groups in cancer development in precancerous lesions. This study was approved by the IRB of the NTUH.
Results:
The difference of p53 and PTTG1 LI in normal oral mucosa, precancerous lesions and cancers were compared; the expression of these two biomarkers over-expressed with the progression of severity of oral lesions. The p53 LI was 0 in normal oral mucosa, 2.20±0.71 in precancerous lesions and 23.40±5.43 in oral cancer, the difference was significant(p=0.0001). The PTTG1 LI was also significantly different and was 32.50±9.05, 68.2±9.1 and 85.5±2.68 respectively for normal oral mucosa, precancerous lesions and cancer (p=0.0001). After adjusting possible confounding factors, the expression of p53 and PTTG1 still showed a significant increase with the progression of oral epithelial lesions. Twenty patients in 82 oral precancerous lesions had malignant development during follow-up period from 3 to 71 months. The PTTG1 LI was significantly associated with cancer development in precancerous lesions in Cox regression model (Hazard ratio=1.03, 1.00~1.05); PTTGI LI ≧80% had the maximum sensitivity and specificity in predicting malignant development in precancerous lesions. The precancerous lesions were classified as high PTTG1 LI (≧80%) and low PTTG1 LI. The high PTTG1 LI was significantly associated with malignant development in precancerous lesions in multivariate Cox regression analysis (Hazard ratio=4.70, 1.29~7.60, p=0.019). The cancer recurrence and mortality were not associated with these two biomarkers.
Conclusion:
PTTG1 and p53 LI increased from normal oral mucosa to oral precancerous lesions and further increased in oral cancers. PTTG1 LI was an independent prognostic factor in predicting cancer development when oral precancerous lesions occurred. PTTG1 may be a potential prognostic marker in oral precancerous lesions.
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