Miki Atsushi, Matsuda Yoko, Aida Junko, Watanabe Jun, Sanada Yukihiro, Sakuma Yasunaru, Lefor Alan K, Fukushima Noriyoshi, Sata Naohiro, Arai Tomio, Takubo Kaiyo, Ishiwata Toshiyuki
Oncology Pathology, Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, Kagawa.
Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo.
Pancreas. 2022 Jul 1;51(6):678-683. doi: 10.1097/MPA.0000000000002081.
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.
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.
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%.
Telomere shortening occurs with carcinogenesis and aging. A significant reduction of telomere length in IPMNs may be useful for surgical decision making.
术前区分胰腺导管内乳头状黏液性肿瘤（IPMNs）的恶性和良性形式具有挑战性。本研究的目的是调查端粒长度是否与IPMNs的病理分级和年龄相关，并阐明端粒长度作为识别恶性IPMNs标志物的效用。
从28例患者切除术后获取胰腺组织。我们通过定量荧光原位杂交测量了IPMNs肿瘤细胞和正常导管细胞的端粒长度。确定了标准化端粒-着丝粒比率（NTCR）与IPMNs病理分级和年龄的相关性。
NTCR随着IPMNs病理分级的增加而逐渐降低。中、高级别发育异常和腺癌病变中的NTCR明显短于正常胰腺导管（P<0.05）。在多变量分析中，端粒长度与致癌作用最相关。当NTCR的临界值设定为0.74时，检测高级别发育异常和腺癌的敏感性为82.8%，特异性为87.5%。
端粒缩短与致癌作用和衰老有关。IPMNs中端粒长度的显著缩短可能有助于手术决策。
