High expression of both desmoplastic stroma and epithelial to mesenchymal transition markers associate with shorter survival in pancreatic ductal adenocarcinoma

European Journal of Histochemistry

Silvia Cecilia Pacheco-Velázquez¹  Sara Rodríguez-Enríquez¹  Fernando Candanedo-González²  Jazmín De Anda-González²  Marco Velasco-Velázquez³  Luis Enrique García-Rios⁴  Rafael Medrano-Guzmán⁴  Héctor Mayani⁵  Alberto Monroy-García⁶  Alejandro Gómez-Delgado⁷  Damián Sánchez-Ramírez⁸  Ana Karen Martínez-Lara⁸  Juan José Montesinos⁸  Patricia Piña-Sánchez⁹  Vadim Pérez-Koldenkova^1,10  Marcos Gutiérrez-de la Barrera^1,11 

[1] Department of Biochemistry, National Institute of Cardiology Ignacio Chávez, Mexico City;Department of Pathology, Oncology Hospital, High Specialty Medical Unit (UMAE), National Medical Center, IMSS, Mexico City;Department of Pharmacology and Peripheral Research Unit in Translational Biomedicine (CMN 20 de noviembre, ISSSTE), School of Medicine, UNAM, Mexico City;Department of Sarcomas, Oncology Hospital, High Specialty Medical Unit (UMAE), National Medical Center, IMSS, Mexico City;Hematopoietic Stem Cells Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center, IMSS, Mexico City;Immunology and Cancer Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center (IMSS), Mexico City;Infectious and Parasitic Diseases, Medical Research Unit, Pediatric Hospital, National Medical Center, IMSS, Mexico City;Mesenchymal Stem Cells Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center, IMSS, Mexico City;Molecular Oncology Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center, IMSS, Mexico City;National Laboratory of Advanced Microscopy-IMSS, National Medical Center, Siglo XXI IMSS, Mexico City;Oncology Research Unit, Oncology Hospital, National Medical Center, IMSS, Mexico City;

关键词: pancreatic ductal adenocarcinoma;    desmoplastic stroma;    epithelial-to-mesenchymal transition;    clinical stage;    degree of tumor differentiation;    survival;   

DOI  :  10.4081/ejh.2022.3360

来源: DOAJ

【 摘 要 】

Desmoplastic stroma (DS) and the epithelial-to-mesenchymal transition (EMT) play a key role in pancreatic ductal adenocarcinoma (PDAC) progression. To date, however, the combined expression of DS and EMT markers, and their association with variations in survival within each clinical stage and degree of tumor differentiation is unknown. The purpose of this study was to investigate the association between expression of DS and EMT markers and survival variability in patients diagnosed with PDAC. We examined the expression levels of DS markers alpha smooth muscle actin (α-SMA), fibronectin, and vimentin, and the EMT markers epithelial cell adhesion molecule (EPCAM), pan-cytokeratin, and vimentin, by immunohistochemistry using a tissue microarray of a retrospective cohort of 25 patients with PDAC. The results were examined for association with survival by clinical stage and by degree of tumor differentiation. High DS markers expression -α-SMA, fibronectin, and vimentin- was associated with decreased survival at intermediate and advanced clinical stages (p=0.006-0.03), as well as with both poorly and moderately differentiated tumor grades (p=0.01-0.02). Interestingly, the same pattern was observed for EMT markers, i.e., EPCAM, pan-cytokeratin, and vimentin (p=0.00008-0.03). High expression of DS and EMT markers within each clinical stage and degree of tumor differentiation was associated with lower PDAC survival. Evaluation of these markers may have a prognostic impact on survival time variation in patients with PDAC.

【 授权许可】

Unknown