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Detailed analysis of epithelial‐mesenchymal transition and tumor budding identifies predictors of long‐term survival in pancreatic ductal adenocarcinoma
Author(s) -
Kohler Ilona,
Bronsert Peter,
Timme Sylvia,
Werner Martin,
Brabletz Thomas,
Hopt Ulrich Theodor,
Schilling Oliver,
Bausch Dirk,
Keck Tobias,
Wellner Ulrich Friedrich
Publication year - 2015
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12752
Subject(s) - tumor budding , vimentin , epithelial–mesenchymal transition , medicine , immunohistochemistry , cytokeratin , pathology , pancreatic cancer , adenocarcinoma , oncology , metastasis , lymph node , cancer , cancer research , lymph node metastasis
Background and Aim Pancreatic ductal adenocarcinoma ( PDAC ) is characterized by aggressive biology and poor prognosis even after resection. Long‐term survival is very rare and cannot be reliably predicted. Experimental data suggest an important role of epithelial‐mesenchymal transition ( EMT ) in invasion and metastasis of PDAC . Tumor budding is regarded as the morphological correlate of local invasion and cancer cell dissemination. The aim of this study was to evaluate the biological and prognostic implications of EMT and tumor budding in PDAC of the pancreatic head. Methods Patients were identified from a prospectively maintained database, and baseline, operative, histopathological, and follow‐up data were extracted. Serial tissue slices stained for Pan‐Cytokeratin served for analysis of tumor budding, and E ‐Cadherin, Beta‐Catenin, and Vimentin staining for analysis of EMT . Baseline, operative, standard pathology, and immunohistochemical parameters were evaluated for prediction of long‐term survival (≥ 30 months) in uni‐ and multivariate analysis. Results Intra‐ and intertumoral patterns of EMT marker expression and tumor budding provide evidence of partial EMT induction at the tumor–host interface. Lymph node ratio and E ‐Cadherin expression in tumor buds were independent predictors of long‐term survival in multivariate analysis. Conclusions Detailed immunohistochemical assessment confirms a relationship between EMT and tumor budding at the tumor–host interface. A small group of patients with favorable prognosis can be identified by combined assessment of lymph node ratio and EMT in tumor buds.