Phenotypical characteristics of undifferentiated carcinoma of the pancreas: A comparison with pancreatic ductal adenocarcinoma and relevance of E-cadherin, α catenin and β catenin expression

Author(s):  
Hirotoshi Yonemasu ◽  
Masaki Takashima ◽  
Ken-Ichi Nishiyama ◽  
Takashi Ueki ◽  
Takashi Yao ◽  
...  
2009 ◽  
Vol 22 (5) ◽  
pp. 651-659 ◽  
Author(s):  
Jonathan R Brody ◽  
Christina L Costantino ◽  
Magdalena Potoczek ◽  
Joseph Cozzitorto ◽  
Peter McCue ◽  
...  

Pancreatology ◽  
2012 ◽  
Vol 12 (3) ◽  
pp. e5
Author(s):  
Nigel B. Jamieson ◽  
Karin A. Oien ◽  
Euan J. Dickson ◽  
Colin J. McKay ◽  
C. Ross Carter

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Thomas Große-Steffen ◽  
Thomas Giese ◽  
Nathalia Giese ◽  
Thomas Longerich ◽  
Peter Schirmacher ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) is frequently associated with fibrosis and a prominent inflammatory infiltrate in the desmoplastic stroma. Moreover, in PDAC, an epithelial-to-mesenchymal transition (EMT) is observed. To explore a possible connection between the infiltrating cells, particularly the polymorphonuclear neutrophils (PMN) and the tumor cell transition, biopsies of patients with PDAC (n=115) were analysed with regard to PMN infiltration and nuclear expression ofβ-catenin and of ZEB1, well-established indicators of EMT. In biopsies with a dense PMN infiltrate, a nuclear accumulation ofβ-catenin and of ZEB1 was observed. To address the question whether PMN could induce EMT, they were isolated from healthy donors and were cocultivated with pancreatic tumor cells grown as monolayers. Rapid dyshesion of the tumor cells was seen, most likely due to an elastase-mediated degradation of E-cadherin. In parallel, the transcription factor TWIST was upregulated,β-catenin translocated into the nucleus, ZEB1 appeared in the nucleus, and keratins were downregulated. EMT was also induced when the tumor cells were grown under conditions preventing attachment to the culture plates. Here, also in the absence of elastase, E-cadherin was downmodulated. PMN as well as prevention of adhesion induced EMT also in liver cancer cell line. In conclusion, PMN via elastase induce EMTin vitro, most likely due to the loss of cell-to-cell contact. Because in pancreatic cancers the transition to a mesenchymal phenotype coincides with the PMN infiltrate, a contribution of the inflammatory response to the induction of EMT and—by implication—to tumor progression is possible.


2021 ◽  
Author(s):  
Ignacio Guillermo Merlo ◽  
Victoria Ardiles ◽  
Rodrigo Sanchez-Clariá ◽  
Eugenia Fratantoni ◽  
Eduardo de Santibañes ◽  
...  

Abstract Background: The aim of this study is to analyze the role of neutrophil-lymphocyte ratio and its variation pre and post-operatively (delta NLR) in overall survival after pancreatectomy for pancreatic ductal adenocarcinoma at a single centre and to identify factors associated with overall survival.Methods: A retrospective study of consecutive patients undergoing pancreatic resection due to PDAC or undifferentiated carcinoma from January 2010 to January 2020 was performed. Association between evaluated factors and overall survival were analyzed using a log-rank test and Cox proportional hazard regression model.Results: Overall, 242 patients underwent complete pancreatic resection for PDAC or undifferentiated carcinoma. OS was 22.8 months (95% CI: 19.5-29) and survival rates at 1, 3 and 5 years were 72%, 32.5% and 20.8% respectively. NLR and delta NLR were not significantly associated with survival (HR=1.14, 95%CI: 0.77-1.68, p=0.5). Lymph node ratio was significantly associated (HR=1.66, 95%CI: 1.21-2.26, p=0.001) in the bivariate analysis. In multivariable analysis the only factors that were significantly associated with survival were perineural invasion (HR=1.94, 95%CI: 1.21-3.14, p=0.006), surgical margin (HR=1.83, 95%CI: 1.10-3.02, p=0.019), tumor size (HR=1.01, 95%CI: 1.003-1.027, p=0.16), postoperative CA 19-9 level (HR=1.001, p<0.001), and completion of adjuvant treatment (HR=0.53, 95%CI: 0.35-0.8, p=0.002).Conclusion: Neutrophil-lymphocyte ratio and delta NLR were not associated with overall survival in this cohort. Risk factors such as perineural invasion, surgical margins, CA19-9 level and tumor size showed worse survival in this study, whereas completing adjuvant treatment was a protective factor.


Surgery ◽  
2015 ◽  
Vol 158 (6) ◽  
pp. 1564-1572 ◽  
Author(s):  
Alexander P. Stark ◽  
Hui-Hua Chang ◽  
Xiaoman Jung ◽  
Aune Moro ◽  
Kathleen Hertzer ◽  
...  

2018 ◽  
Vol 18 (3) ◽  
pp. 246-251 ◽  
Author(s):  
Petra Radulović ◽  
Božo Krušlin

Extensive research is being conducted to identify novel diagnostic, predictive and prognostic biomarkers for pancreatic ductal adenocarcinoma (PDAC), as only a few markers have been routinely used so far with limited success. Our aim was to assess the expression of neural precursor cell expressed developmentally down-regulated protein 9 (NEDD9), E-cadherin, and γ-catenin in PDAC in relation to clinicopathological parameters and patient survival. We also investigated if there is a correlation of NEDD9 expression with E-cadherin or γ-catenin. The protein expression was determined by immunohistochemistry in 61 PDAC and 61 samples of normal pancreatic tissue. The log rank test and Kaplan-Meier survival curve were used for survival analysis. E-cadherin and γ-catenin expressions were reduced in PDAC, and completely retained in normal pancreatic tissue. Expression of NEDD9 was significantly increased in PDAC (strong expression in 78.7% of cases and moderate in 21.3%) and reduced in normal pancreatic tissue (strong positivity in 45.9% of cases, moderate in 31.1%, and weak in 23%). There was a positive correlation between reduced E-cadherin and γ-catenin expression in PDAC (p = 0.015). The loss or reduced expression of E-cadherin had a negative impact on patient survival (p = 0.020). A negative correlation between E-cadherin expression and tumor grade was also observed (p = 0.011). Decreased E-cadherin expression was more common in male patients with PDAC (81.3% vs. 60% for females, p = 0.005). γ-catenin and NEDD9 expressions were not statistically correlated with tumor stage and grade, gender, nor with patient survival. Our results support the role of NEDD9, E-cadherin and γ-catenin proteins in PDAC, but further research should clarify in detail their mechanism of action in pancreatic cancer.


2016 ◽  
Vol 70 (7) ◽  
pp. 619-624 ◽  
Author(s):  
Aya Kawanishi ◽  
Kenichi Hirabayashi ◽  
Misuzu Yamada ◽  
Yumi Takanashi ◽  
Atsuko Hadano ◽  
...  

AimsThe loss, or decreased expression, of nectin-like molecule 4 (Necl-4; an immunoglobulin-like cell adhesion molecule) is reported to be associated with the development and progression of certain types of cancer. We investigated the clinicopathological significance of Necl-4 expression in patients with pancreatic ductal adenocarcinoma (PDAC).MethodsImmunohistochemical analyses of Necl-4 (n=258) and E-cadherin (n=256) expression were performed using tissue microarray blocks of PDAC samples. Necl-4 expression of 38 pancreatic intraepithelial neoplasia (PanIN) lesions included in tissue microarray cores was also evaluated. Necl-4 and E-cadherin expression was considered positive if >30% of cells were stained, and negative if ≤30% of cells were stained.ResultsNecl-4 expression was positive in 45.7% (n=118) and negative in 54.3% (n=140) of PDAC cases. Necl-4 staining was positive in 96.7% (n=29) and negative in 3.3% (n=1) of low-grade PanIN cases, and positive in 62.5% (n=5) and negative in 37.5% (n=3) of high-grade PanIN cases. The number of cases with positive Necl-4 expression decreased in the order low-grade PanIN>high-grade PanIN>PDAC (p<0.001). Negative Necl-4 expression was significantly associated with a larger tumour size of >30 mm, perineural invasion, lymphatic involvement, lymph node metastasis (pN1), an advanced TNM (tumour, node, metastases) stage (stage IIB–IV), an advanced histological grade (G2/3), and shorter overall survival. E-cadherin staining was positive in 46.1% (n=118) and negative in 53.9% (n=138) of PDAC cases. Necl-4 expression correlated positively with E-cadherin expression (r=0.405, p<0.001).ConclusionsThe results suggest that Necl-4 is associated with carcinogenesis and aggressiveness of PDAC.


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