Ezzeddine Chouat1, Alia Zehani2, Ines Chelly2, Manel Njima3, Houcine Maghrebi4, Mohammed Amine Bani2, Leila Njim3, Abdelfatteh Zakhama3, Slim Haouet2, Nidhameddine Kchir2. 1. Department of Pathology, Rabta University Hospital, Rabta Jebbari, 1007 Tunis, Tunisia. Electronic address: ch.ezzeddine@gmail.com. 2. Department of Pathology, Rabta University Hospital, Rabta Jebbari, 1007 Tunis, Tunisia. 3. Department of Pathology, Fattouma Bourguiba University Hospital, 1st June 1955 Street, 5000 Monastir, Tunisia. 4. Department of Surgery A, Rabta University Hospital, Rabta Jebbari, 1007 Tunis, Tunisia.
Abstract
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a devastatingly poor prognosis. Surgical resection is undertaken in only 20% of patients. Most of well-known prognostic factors reflect tumor stage more than its biology. So it is important to identify new biological indicators related to survival in order to develop new therapies. OBJECTIVE: To determine the relation between tumor budding and Epithelial Mesenchymal Transition (EMT) and to evaluate their impact on survival for patients after resection of PDAC. METHODS: We herein report a retrospective study of 50 patients with resected PDAC. Tumor budding, immunohistochemical expression of vimentin and other standard factors were correlated with survival using the Kaplan-Meier method and Cox multivariable survival analysis. For tumor budding assessment, an inter-observer variability study was performed using 100 images of tumor slides stained with Hematoxylin & Eosin and Pan-Cytokeratin. RESULTS: Tumor budding was present in all tumors. A substantial agreement between six pathologists was established in distinguishing high-grade from low-grade budding (κ = 0.6 and 0.73 for H&E and PCK images respectively). High-grade budding was identified in 56% of tumors (28/50). It was an adverse prognostic factor independent of tumor size, resection margins status, nodal status and vascular invasion (p = 0.008). Tumor budding was significantly associated with vimentin expression (p = 0.002). CONCLUSIONS: The association of tumor budding with vimentin expression supported the idea that EMT is a key process in PDAC responsible for progression and drug resistance. Consequently, the elucidation of EMT molecular biology and development of new targeted therapy may improve disease outcome.
BACKGROUND:Pancreatic ductal adenocarcinoma (PDAC) has a devastatingly poor prognosis. Surgical resection is undertaken in only 20% of patients. Most of well-known prognostic factors reflect tumor stage more than its biology. So it is important to identify new biological indicators related to survival in order to develop new therapies. OBJECTIVE: To determine the relation between tumor budding and Epithelial Mesenchymal Transition (EMT) and to evaluate their impact on survival for patients after resection of PDAC. METHODS: We herein report a retrospective study of 50 patients with resected PDAC. Tumor budding, immunohistochemical expression of vimentin and other standard factors were correlated with survival using the Kaplan-Meier method and Cox multivariable survival analysis. For tumor budding assessment, an inter-observer variability study was performed using 100 images of tumor slides stained with Hematoxylin & Eosin and Pan-Cytokeratin. RESULTS:Tumor budding was present in all tumors. A substantial agreement between six pathologists was established in distinguishing high-grade from low-grade budding (κ = 0.6 and 0.73 for H&E and PCK images respectively). High-grade budding was identified in 56% of tumors (28/50). It was an adverse prognostic factor independent of tumor size, resection margins status, nodal status and vascular invasion (p = 0.008). Tumor budding was significantly associated with vimentin expression (p = 0.002). CONCLUSIONS: The association of tumor budding with vimentin expression supported the idea that EMT is a key process in PDAC responsible for progression and drug resistance. Consequently, the elucidation of EMT molecular biology and development of new targeted therapy may improve disease outcome.
Authors: Alessandro Lugli; Inti Zlobec; Martin D Berger; Richard Kirsch; Iris D Nagtegaal Journal: Nat Rev Clin Oncol Date: 2020-09-08 Impact factor: 66.675
Authors: Minhua Wang; Jeannelyn S Estrella; Matthew H Katz; Michael Kim; Asif Rashid; Jeffrey E Lee; Anirban Maitra; Ignacio I Wistuba; Robert A Wolff; Gauri R Varadhachary; Huamin Wang Journal: Pancreas Date: 2019 Nov/Dec Impact factor: 3.243
Authors: Siyuan Zeng; Marina Pöttler; Bin Lan; Robert Grützmann; Christian Pilarsky; Hai Yang Journal: Int J Mol Sci Date: 2019-09-11 Impact factor: 5.923