Department of Pathology, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Hum Pathol. 2024 Oct;152:105653. doi: 10.1016/j.humpath.2024.105653. Epub 2024 Aug 28.
Mucinous cystic neoplasm (MCN) is one of the precursor lesions of pancreatic ductal adenocarcinoma and intrahepatic cholangiocarcinoma. The aim of this study is to examine the presence of short telomeres in promoting the tumorigenesis of MCN by measuring telomere lengths in distinct components of MCN, including the mucinous lining epithelium, non-mucinous lining epithelium, and ovarian-type stroma. A total of 45 patients with MCN (30 pancreatic and 15 hepatic cases) were obtained. Quantitative telomere-specific fluorescent in situ hybridization was performed to measure the telomere length of specific cell types within MCNs, including mucinous lining epithelium, non-mucinous lining epithelium, and ovarian-type stroma, as well as normal ductal epithelium and adenocarcinoma. Relative telomere lengths tended to decrease between normal ductal epithelium, ovarian-type stroma, non-mucinous lining epithelium, mucinous lining epithelium, and adenocarcinoma regardless of the involved organs. Among the analyzed cell types, relative telomere lengths were significantly different between normal ductal epithelium (3.31 ± 0.78), ovarian-type stroma (2.90 ± 0.93), non-mucinous lining epithelium (2.84 ± 0.79), mucinous lining epithelium (2.49 ± 0.93), and adenocarcinoma (1.19 ± 0.59), respectively (P < 0.001, mixed-effects model). As expected, no difference in relative telomere lengths was observed between normal ductal epithelium and ovarian-type stroma; however, significant differences were observed in pair-wise comparisons between ovarian-type stroma vs. non-mucinous lining epithelium (P = 0.001), non-mucinous lining epithelium vs. mucinous lining epithelium (P = 0.005), and mucinous lining epithelium vs. adenocarcinoma (P < 0.001). These findings suggest gradual telomere shortening occurs in the tumorigenesis of MCN, which may have important implications for the progression of this disease.
黏液性囊性肿瘤（MCN）是胰腺导管腺癌和肝内胆管细胞癌的前体病变之一。本研究旨在通过测量 MCN 不同成分中的端粒长度，检查短端粒在促进 MCN 肿瘤发生中的作用，这些成分包括黏液性衬里上皮、非黏液性衬里上皮和卵巢型基质。共获得 45 例 MCN 患者（30 例胰腺和 15 例肝）。采用定量端粒特异性荧光原位杂交技术测量 MCN 中特定细胞类型的端粒长度，包括黏液性衬里上皮、非黏液性衬里上皮和卵巢型基质，以及正常导管上皮和腺癌。无论涉及的器官如何，正常导管上皮、卵巢型基质、非黏液性衬里上皮、黏液性衬里上皮和腺癌之间的相对端粒长度都有下降的趋势。在所分析的细胞类型中，正常导管上皮（3.31±0.78）、卵巢型基质（2.90±0.93）、非黏液性衬里上皮（2.84±0.79）、黏液性衬里上皮（2.49±0.93）和腺癌（1.19±0.59）之间的相对端粒长度差异具有统计学意义（P<0.001，混合效应模型）。正如预期的那样，正常导管上皮和卵巢型基质之间的相对端粒长度没有差异；然而，在卵巢型基质与非黏液性衬里上皮（P=0.001）、非黏液性衬里上皮与黏液性衬里上皮（P=0.005）和黏液性衬里上皮与腺癌（P<0.001）之间的两两比较中观察到显著差异。这些发现表明，MCN 的肿瘤发生中存在逐渐的端粒缩短，这可能对该疾病的进展具有重要意义。
