Prognostic significance of telomerase activity and human telomerase reverse transcriptase expression in ampullary carcinoma.
BACKGROUND
Telomerase activity and human telomerase reverse transcriptase (TERT) have been reported as markers of tumor aggressiveness and poor prognosis in several digestive cancers. In the present study, we examined telomerase activity and TERT expression in ampullary carcinoma to determine whether these parameters could be used as indicators of aggressiveness and prognosis.


METHODS
Telomerase activity was analyzed by using the telomeric repeat amplification protocol assay, and TERT was examined by immunohistochemistry in ampullary carcinoma tissue samples resected from 46 patients.


RESULTS
Telomerase activity was detected in 42 (91.3%) ampullary carcinomas and 27 (58.7%) showed high activity, whereas TERT expression was detected in 35 (76.1%), including 21 with weak expression and 14 with strong expression. Univariate analysis revealed that histological grade (P = 0.029), tumor depth (P < 0.001), nodal status (P = 0.013), UICC stage (P = 0.009), perineural invasion (P < 0.001), and telomerase activity (P = 0.031) were significantly associated with disease-specific survival. In multivariate analysis, only telomerase activity remained an independent predictor of prognosis (P = 0.043). There was no statistical significance for survival among the three grades of TERT expression (P = 0.054); however, in subgroup analysis, patients with strong TERT expression showed significantly poorer prognosis than those without TERT expression (P = 0.013).


CONCLUSIONS
Our results suggest that high telomerase activity and strong TERT expression may serve as new prognostic markers for evaluating the prognosis of patients with resected ampullary carcinoma.
Department of Surgery, Division of Clinical Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. ryusakabe@hiroshima-u.ac.jp
Ryutaro
R
Sakabe
Yoshiaki
Y
Murakami
Kenichiro
K
Uemura
Takeshi
T
Sudo
Yasushi
Y
Hashimoto
Naru
N
Kondo
Akira
A
Nakashima
Hiroki
H
Ohge
Taijiro
T
Sueda
Eiso
E
Hiyama
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater / Q000378:metabolism / Q000473:pathology*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000201:enzymology* / Q000473:pathology* / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D003138:Common Bile Duct Neoplasms / Q000201:enzymology* / Q000473:pathology* / Q000628:therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004338:Drug Combinations; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage; D016577:Pancreaticoduodenectomy; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D005641:Tegafur / Q000008:administration & dosage; D019098:Telomerase / Q000378:metabolism*; D055815:Young Adult; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D019098:Telomerase; D000093542:Gemcitabine