Yu-Wen Tien1, Hung-Jen Chien2, Tsai-Chen Chiang1, Mei-Hsin Chung2,3, Chih-Yuan Lee1, Shih-Jung Peng4, Chien-Chia Chen1, Ya-Hsien Chou2,4, Fu-Ting Hsiao2, Yung-Ming Jeng5, Shiue-Cheng Tang6,7. 1. Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan. 2. Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan. 3. Department of Pathology, National Taiwan University Hospital - Hsinchu Branch, Hsinchu, Taiwan. 4. Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan. 5. Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan. 6. Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan. sctang@life.nthu.edu.tw. 7. Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan. sctang@life.nthu.edu.tw.
Abstract
AIMS/HYPOTHESIS: Islets are thought to be stably present in the adult human pancreas to maintain glucose homeostasis. However, identification of the pancreatic intraepithelial neoplasia (PanIN)-islet complex in mice and the presence of PanIN lesions in adult humans suggest that similar remodelling of islet structure and environment may occur in the human pancreas. To identify islet remodelling in a clinically related setting, we examine human donor pancreases with 3D histology to detect and characterise the human PanIN-islet complex. METHODS: Cadaveric donor pancreases (26-65 years old, n = 10) were fixed and sectioned (350 μm) for tissue labelling, clearing and microscopy to detect local islet remodelling for 3D analysis of the microenvironment. The remodelled microenvironment was subsequently examined via microtome-based histology for clinical assessment. RESULTS: In nine pancreases, we identified the unique peri-lobular islet aggregation associated with the PanIN lesion (16 lesion-islet complexes detected; size: 3.18 ± 1.34 mm). Important features of the lesion-islet microenvironment include: (1) formation of intra-islet ducts, (2) acinar atrophy, (3) adipocyte association, (4) inflammation (CD45+), (5) stromal accumulation (α-SMA+), (6) increase in Ki-67 proliferation index but absence of Ki-67+ alpha/beta cells and (7) in-depth and continuous duct-islet cell contacts, forming a cluster. The duct-islet cell cluster and intra-islet ducts suggest likely islet cell neogenesis but not replication. CONCLUSIONS/ INTERPRETATION: We identify local islet remodelling associated with PanIN-islet complex in the adult human pancreas. The tissue remodelling and the evidence of inflammation and stromal accumulation suggest that the PanIN-islet complex is derived from tissue repair after a local injury.
AIMS/HYPOTHESIS: Islets are thought to be stably present in the adult human pancreas to maintain glucose homeostasis. However, identification of the pancreatic intraepithelial neoplasia (PanIN)-islet complex in mice and the presence of PanIN lesions in adult humans suggest that similar remodelling of islet structure and environment may occur in the human pancreas. To identify islet remodelling in a clinically related setting, we examine human donor pancreases with 3D histology to detect and characterise the human PanIN-islet complex. METHODS: Cadaveric donor pancreases (26-65 years old, n = 10) were fixed and sectioned (350 μm) for tissue labelling, clearing and microscopy to detect local islet remodelling for 3D analysis of the microenvironment. The remodelled microenvironment was subsequently examined via microtome-based histology for clinical assessment. RESULTS: In nine pancreases, we identified the unique peri-lobular islet aggregation associated with the PanIN lesion (16 lesion-islet complexes detected; size: 3.18 ± 1.34 mm). Important features of the lesion-islet microenvironment include: (1) formation of intra-islet ducts, (2) acinar atrophy, (3) adipocyte association, (4) inflammation (CD45+), (5) stromal accumulation (α-SMA+), (6) increase in Ki-67 proliferation index but absence of Ki-67+ alpha/beta cells and (7) in-depth and continuous duct-islet cell contacts, forming a cluster. The duct-islet cell cluster and intra-islet ducts suggest likely islet cell neogenesis but not replication. CONCLUSIONS/ INTERPRETATION: We identify local islet remodelling associated with PanIN-islet complex in the adult human pancreas. The tissue remodelling and the evidence of inflammation and stromal accumulation suggest that the PanIN-islet complex is derived from tissue repair after a local injury.
Authors: R H Hruban; N V Adsay; J Albores-Saavedra; C Compton; E S Garrett; S N Goodman; S E Kern; D S Klimstra; G Klöppel; D S Longnecker; J Lüttges; G J Offerhaus Journal: Am J Surg Pathol Date: 2001-05 Impact factor: 6.394
Authors: Susan C Abraham; Robb E Wilentz; Charles J Yeo; Taylor A Sohn; John L Cameron; John K Boitnott; Ralph H Hruban Journal: Am J Surg Pathol Date: 2003-01 Impact factor: 6.394
Authors: M Van de Casteele; G Leuckx; L Baeyens; Y Cai; Y Yuchi; V Coppens; S De Groef; M Eriksson; C Svensson; U Ahlgren; J Ahnfelt-Rønne; O D Madsen; A Waisman; Y Dor; J N Jensen; H Heimberg Journal: Cell Death Dis Date: 2013-03-07 Impact factor: 8.469