AIMS: Pancreatic ductal adenocarcinoma follows a multistep model of progression through precursor lesions called pancreatic intraepithelial neoplasia (PanIN). The high mobility group A1 (HMGA1) and high mobility group A2 (HMGA2) proteins are architectural transcription factors that have been implicated in the pathogenesis and progression of malignant tumours, including pancreatic cancer. The aim of this study was to explore the role of HMGA1 and HMGA2 in pancreatic carcinogenesis. METHODS AND RESULTS: HMGA1 and HMGA2 expression was examined in 210 ductal pancreatic adenocarcinomas from resection specimens, combined on a tissue microarray also including 40 examples of PanIN and 40 normal controls. The results were correlated with the clinicopathological parameters of the tumours and the outcome of the patients. The percentage of tumour cells showing HMGA1 and HMGA2 nuclear immunoreactivity correlated positively with increasing malignancy grade and lymph node metastasis. Moreover, HMGA1 and HMGA2 expression was significantly higher in invasive carcinomas than in PanINs. No, or very low, expression was found in normal pancreatic tissue. CONCLUSIONS: Our results suggest that HMGA1 and HMGA2 are implicated in pancreatic carcinogenesis and may play a role in tumour progression towards a more malignant phenotype.
AIMS: Pancreatic ductal adenocarcinoma follows a multistep model of progression through precursor lesions called pancreatic intraepithelial neoplasia (PanIN). The high mobility group A1 (HMGA1) and high mobility group A2 (HMGA2) proteins are architectural transcription factors that have been implicated in the pathogenesis and progression of malignant tumours, including pancreatic cancer. The aim of this study was to explore the role of HMGA1 and HMGA2 in pancreatic carcinogenesis. METHODS AND RESULTS:HMGA1 and HMGA2 expression was examined in 210 ductal pancreatic adenocarcinomas from resection specimens, combined on a tissue microarray also including 40 examples of PanIN and 40 normal controls. The results were correlated with the clinicopathological parameters of the tumours and the outcome of the patients. The percentage of tumour cells showing HMGA1 and HMGA2 nuclear immunoreactivity correlated positively with increasing malignancy grade and lymph node metastasis. Moreover, HMGA1 and HMGA2 expression was significantly higher in invasive carcinomas than in PanINs. No, or very low, expression was found in normal pancreatic tissue. CONCLUSIONS: Our results suggest that HMGA1 and HMGA2 are implicated in pancreatic carcinogenesis and may play a role in tumour progression towards a more malignant phenotype.
Authors: Guido von Figura; Akihisa Fukuda; Nilotpal Roy; Muluye E Liku; John P Morris Iv; Grace E Kim; Holger A Russ; Matthew A Firpo; Sean J Mulvihill; David W Dawson; Jorge Ferrer; William F Mueller; Anke Busch; Klemens J Hertel; Matthias Hebrok Journal: Nat Cell Biol Date: 2014-02-23 Impact factor: 28.824
Authors: Shin-Heng Chiou; Viviana I Risca; Gordon X Wang; Dian Yang; Barbara M Grüner; Arwa S Kathiria; Rosanna K Ma; Dedeepya Vaka; Pauline Chu; Margaret Kozak; Laura Castellini; Edward E Graves; Grace E Kim; Philippe Mourrain; Albert C Koong; Amato J Giaccia; Monte M Winslow Journal: Cancer Discov Date: 2017-08-08 Impact factor: 39.397
Authors: Sita Kugel; Carlos Sebastián; Julien Fitamant; Kenneth N Ross; Supriya K Saha; Esha Jain; Adrianne Gladden; Kshitij S Arora; Yasutaka Kato; Miguel N Rivera; Sridhar Ramaswamy; Ruslan I Sadreyev; Alon Goren; Vikram Deshpande; Nabeel Bardeesy; Raul Mostoslavsky Journal: Cell Date: 2016-05-12 Impact factor: 41.582
Authors: Christopher J DiMaio; Frances Weis-Garcia; Emilia Bagiella; Laura H Tang; Peter J Allen Journal: Gastrointest Endosc Date: 2015-09-25 Impact factor: 9.427