Telomere Attrition in Intraductal Papillary Mucinous Neoplasms of the Pancreas Associated With Carcinogenesis and Aging

Abstract

Objectives: It is challenging to preoperatively distinguish malignant and benign forms of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. The aims of this study were to investigate whether telomere length is associated with pathological grade of IPMNs and age and to clarify the utility of telomere length as a marker to identify malignant IPMNs.Methods: Pancreas tissue was obtained from 28 patients after resection.We measured the telomere lengths of tumor cells in IPMNs and normal duct cells by quantitative fluorescence in situ hybridization. The association of normalized telomere-centromere ratio (NTCR) to pathological grade of IPMNs and age were determined. Results:The NTCR showed a gradual decrease with increasing pathological grade of IPMNs. The NTCR in intermediate-and high-grade dysplasia and adenocarcinoma lesions was significantly shorter than in normal pancreatic ducts (P < 0.05). In multivariate analysis, telomere length was most associated with carcinogenesis. When the cutoff value of NTCR was set to 0.74, the sensitivity for detection of high-grade dysplasia and adenocarcinoma was 82.8%, with a specificity of 87.5%. Conclusions:Telomere shortening occurs with carcinogenesis and aging. A significant reduction of telomere length in IPMNs may be useful for surgical decision making.

Understanding, diagnosing, and treating pancreatic cancer from the perspective of telomeres and telomerase

“…In PanIN and IPMN, there are many changes in the epithelial cells affected by the disease, one of which is the presence of telomere shortening [33,34]. Other studies have shown that the telomerecentromere ratio (TRC) decreases as the pathological grade of IPMN increases [35]. This suggests that telomeres become progressively shorter as the disease progresses.…”

“…Its specific anticancer mechanisms include inhibition of HIF-1α、regulation of VEGF/VEGFR-2 signalling pathway that inhibits angiogenesis and selectively stimulates the Gαs/cAMP pathway that inhibits cancer cell proliferation, and so on. However, The NTCR showed a gradual decrease with increasing pathological grade of IPMNs [35] The sample size only includes the number of samples related to pancreatic lesions in the study and the control group.…”