Telomerase activity and patient survival after surgery for gastric and oesophageal cancer.
OBJECTIVE
The ribonucleoprotein telomerase extends telomeres in cancer cells and has been proposed as a prognostic marker for cancer. We measured telomerase expression in proximal adenocarcinomas (those arising in the distal oesophagus or at the gastro-oesophageal junction) and distal adenocarcinomas (those arising in the corpus or antrum of the stomach) of the foregut, and correlated telomerase activity with pathological stage and post-operative survival.


METHODS
Surgical specimens were collected from patients undergoing resections for gastric and oesophageal carcinomas. Haematoxylin and eosin histology provided data on the pathological tumour stage and pathological node stage.


METHODS
The telomerase activity of cancer specimens was determined using the telomeric repeat amplification protocol. A single pathologist, blinded to the results of the telomerase assays, reviewed all slides of cancers to assign T and N stages.


RESULTS
The cancers exhibited a wide range of telomerase expression. There was no significant difference between the telomerase activity of proximal adenocarcinomas (median, 551 U; 95% confidence interval, 154-2394 U; n = 26) and distal adenocarcinomas (median, 703 U; 95% confidence interval, 139-1618 U; n = 20). Distal adenocarcinomas expressing high telomerase activity (greater than the median) were significantly more advanced with regard to T stage than distal cancers expressing low telomerase levels (less than the median; P = 0.03, Mann-Whitney test). In distal adenocarcinomas, high telomerase activity was associated with poor patient survival (median 3 months) compared to low telomerase activity (median survival 22.4 months; P = 0.01, log-rank test). No such differences were observed for proximal adenocarcinomas.


CONCLUSIONS
There is a difference between gastric and oesophageal/gastro-oesophageal junction adenocarcinomas in terms of the relationship with telomerase expression and clinico-pathological variables. Among patients with distal gastric adenocarcinoma, telomerase activity correlates with markers of advanced disease, whereas this relationship does not hold true in oesophageal/gastro-oesophageal junction adenocarcinomas. Telomerase activation may occur at different stages of the formation of the malignant phenotype in these two cancers and may reflect differences in their pathogenesis. Telomerase could be a prognostic marker in gastric but not in oesophageal adenocarcinoma.
Usselmann
B
B
Department of Gastroenterology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK.
Newbold
M
M
Morris
A G
AG
Nwokolo
C U
CU
D000230:Adenocarcinoma / Q000201:enzymology / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D014408:Biomarkers, Tumor / Q000032:analysis*; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D004943:Esophagogastric Junction; D006801:Humans; D011379:Prognosis; D013274:Stomach Neoplasms / Q000201:enzymology / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D015996:Survival Rate; D019098:Telomerase / Q000032:analysis*
D014408:Biomarkers, Tumor; D019098:Telomerase