Clinical implications of telomerase activity in oral squamous cell carcimoma

Shim, Yu Jin; Kim, Myung Jin; Nahm, Dong Seok; Lee, Jong Ho

Abstract

Telomerase is a ribonucleoprotein that synthesizes telomere repeats. It has been reported that activation of telomerase was associtated with immortalization, proliferative activity and carcinogenesis. Recently, telomerase activity has been extensively studied in many kinds of malignant tumors for clinical diagnostic and/or prognostic utilities. In neuroblastoma, breast carcinoma,gastric carcinoma, non-small cell lung carcinoma, close relationship has been reported between high telomerase activity and lymph node metastasis, tumor aggressiveness and poor prognosis. The purpose of this study is to to investigate the clinical implication of telomerase activity assay as an adjunctive factor in decision-making on neck node management, speedy pre-operative judging on histologic malignancy grading. Thus we performed semi-quantitative assay of telomerase activity using Telomerase PCR ELISA kit(Boeringer Manheim , Germany) and evaluated correlation between telomerase activity and tumor size, neck node metastasis, Anneroth malignancy score and influence of pre-operative chemotherapy on its activity in 27 cases of oral squamous cell carcinomas and 18 cases of normal oral epithelium. Also, correlation between telomerase activities and PCNA indices was evaluated. The results were obtained as follows: 1. The telomerase activities were detected in 24 specimens out of 27 oral squamous cell carcinoma specimens (88.9%) and in 5 specimens out of 18 normal oral epithelium specimens (27.8%). The mean value of telomerase activities was 0.9793+/-0.3428 in 24 oral squamous cell carcinoma specimens and 0.4855+/-0.1117 in 5 normal oral epithelium specimens. The positivity rate and mean value of telomerase activities in oral squamous cell carcinoma specimens were significantly higher than those of normal oral epithelium specimens (p<0.05). 2. There was no significant correlation between total Anneroth malignancy score and telomerase activity (p>0.05), but points of mitosis index and depth of invasion were significantly correlated with telomerase activities (p<0.05). 3. The positive immunohistochemical staining for PCNA(proliferating cell nuclear antigen) was observed in 26 specimens out of 27 oral squamous cell carcinoma specimens and mean value of PCNA indices of 26 specimens was 53.67+/-26.46. PCNA indices were significantly correlated with telomerase activities (p<0.05). 4. The mean value of telomerase activities was significantly higher in pathologic T3/T4 group than in T1/T2 group (p<0.01). There was no significant difference of mean value of telomerase activities between pathologic neck node positive group and negative group (p> 0.05). Pre-operative chemotherapy significantly lowered the telomerase activities (p<0.05). The above results suggested telomerase activity could be used as diagnostic marker and adjunctive parameter for judging on histologic malignancy in oral squamous cell carcinoma.