ADVERTISEMENT
The prognostic significance of early expression of epithelial-to-mesenchymal transition markers in resectable pancreatic cancer patients
Background
Pancreatic ductal adenocarcinoma cancer (PDAC) is the seventh leading cause of cancer death worldwide, mainly due to late-stage presentation, therapy resistance and early metastasis. E-cadherin (E-cad), one of the cell-cell adhesion molecules, is regarded as a major suppressor of metastasis and is typically downregulated in most pancreatic tumors. Epithelial to mesenchymal transition (EMT) is characterized by a downregulation in epithelial markers such as E-cad and an upregulation of mesenchymal markers such as Vimentin (Vim). EMT was observed in many tumors originating from epithelial cells, and it is one of the triggers of early progression and metastasis in PDAC. In this study, we are examining the early expression of EMT, described as the total loss of epithelial markers with expression of mesenchymal markers, as predictor of worse survival in patients with resectable PDAC.
Methods
This is a retrospective study involving patients diagnosed with resectable PDAC at the American University of Beirut Medical Center between January 1 2005 and June 30 2019. Out of 137 patients included in the study, we are reporting here the data and immunohistochemical analysis of the first 59 patients. Evaluation was done to document the percentage of stained cells with E-cad and Vim, as well as the staining intensity of E-cad as follows: 0=no stain, 1=weak, 2=moderate, 3=strong. The E-cad percentage score is calculated based on the percentage of E-cad stained cells as follows: 0= 25-50%, 3=>50-75%, 4=>75%. The E-cad score is calculated as E-cad percentage score multiplied by E-cad stain intensity. Finally, the E-cad expression is based on the E-cad score such as Low=1-3 and High=≥4. The Vim expression is based on the percentage of Vim stained cells and is defined as Low= 10%.
Results
Out of the 59 patients included, 33 (55%) were females with median age of all patients is 64 years (range from 37 to 79). 4 patients (7%) had tumor grade 1, 38 (65%) had tumor grade 2 and 17 (28%) had tumor grade 3. 49 patients (83%) had a high E-cad expression and 10 (17%) had a low expression. 19 (32%) had a high Vim expression and 40 (68%) had a low expression. 13 (22%) patients had both E-cad high/Vim high expression and 4 (7%) patients had both low expressions. 36 (61%) patients were E-cad high/Vim low, and 6 (10%) were E-cad low/Vim high. Median overall survival (OS) on 59 patients is 24.4 months. OS of E-cad low is 17.4 months versus OS of all other patients is 25.5 months (p-value=0.7). OS of Vim high patients is 24.2 months versus OS of all other patients is 24.4 months (p-value=0.9). OS of E-cad low/Vim high patients is 21.8 months versus OS of all other patients is 24.5 months (p-value=0.4).
Conclusions
In our study, EMT expression does not play a major role in resectable pancreatic cancer while low E- cad in such category of patients may have a worse survival. A prospective trial is needed to prove the concept.
Legal entity responsible for the study
The author.
Funding
Has not received any funding.
Disclosures
All authors have declared no conflicts of interest.
