Ductal adenocarcinoma of the pancreas: Expression of growth factor receptors, oncogenes and suppressor genes, and their relationship to pathological features, staging and survival

Lozano-León, Antonio; Pérez-Quintela, B. Vieites; Iglesias‐García, Julio; Lariño‐Noia, José; Varó, Evaristo; Forteza, Jerónimo; Domínguez‐Muñoz, J. Enrique

doi:10.3892/ol.2010.206

Cited by 14 publications

(8 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Epidermal growth factor receptor (EGFR) and human EGFR 2 (HER2) and vascular endothelial growth factor receptor (VEGFR) are tyrosine kinase receptors highly expressed in several solid tumors including pancreatic cancer ( Lozano-Leon et al, 2011 ; Karanikas et al, 2016 ). These receptors are frequently reported to harbor aberrant activities that may lead to proliferation, survival, migration and differentiation required for PCa pathogenesis.…”

Section: Resultsmentioning

confidence: 99%

Enhancing efficacy of gemcitabine in pancreatic patient-derived xenograft mouse models

Inkoom

Ndemazie

Affram

et al. 2020

International Journal of Pharmaceutics: X

View full text Add to dashboard Cite

Gemcitabine (Gem), a nucleoside analog, is a preferred choice of treatment for pancreatic cancer (PCa) and often used in combination therapy against wide range of solid tumors. It is known to be rapidly inactivated in blood by cytidine deaminase. The objective of the study was to improve the systemic stability and anticancer activity of modified Gem termed 4-N-stearoylGem (4NSG) In this study, the IC 50 values of 4NSG treated MiaPaCa-2 and primary pancreatic cancer (PPCL-46) cultures were significantly lower when compared with gemcitabine hydrochloride (GemHCl) treated cultures. In acute toxicity study, liver enzyme level of aspartate aminotransferase (AST) of the control mice was not significantly different from AST levels of 4NSG and GemHCl treated mice. However, alanine aminotransferase (ALT) level of control mice (67 ± 5 mUnits/mL) was significantly lower compared with ALT levels of GemHCl (232 ± 28 mUnits/mL) and that of 4NSG (172 ± 22 mUnits/mL) ( p < 0.0001). More importantly, ALT level of 4NSG was lower than ALT level of GemHCl ( p < 0.05). Although ALT levels were elevated, pathological images of liver and kidney tissues of control, GemHCl and 4NSG treated mice revealed no architectural changes and no significant change in mice weight was observed during treatment. The bioavailability (AUC) of 4NSG was 3-fold high and significantly inhibited the tumor growth as compared with equivalent dose of GemHCl. Immunohistochemical staining revealed that 4NSG significantly inhibited the expression vascular endothelial growth factor (VEGF) receptor. The study is unique because it established, for the first time, enhanced anticancer activity of 4NSG against pancreatic patient-derived xenograft (PDX) mouse model and PPCL-46 cells compared with Gem. 4SGN enhanced pharmacokinetic profile and improved the therapeutic efficacy of the standard-of-care Gem. Lastly, 4GSN showed a remarkable tumor growth inhibition and revealed significant antiangiogenic activity in 4GSN treated pancreatic PDX tumor.

show abstract

Section: Resultsmentioning

confidence: 99%

Enhancing efficacy of gemcitabine in pancreatic patient-derived xenograft mouse models

Inkoom

Ndemazie

Affram

et al. 2020

International Journal of Pharmaceutics: X

View full text Add to dashboard Cite

show abstract

“…If less than 400 cells were available in the tissue section, the case was excluded from evaluation of the particular antigen expression. For a case to be considered positive, the relative amount of positive cells had to reach the cut-off value [20][21][22][23][24][25][26][27][28], as shown in Table I. To detect the microvascular density (MVD), the endothelial layer was highlighted by membranous CD34 expression.…”

Section: Immunohistochemical Visualisation and Assessmentmentioning

confidence: 99%

Original paper Morphological and immunohistochemical profile of pancreatic neuroendocrine neoplasms

Simtniece¹,

Vanags²,

Štrumfa³

et al. 2015

pjp

View full text Add to dashboard Cite

The study represents a comprehensive retrospective morphological and immunohistochemical profiling of pancreatic neuroendocrine neoplasms (PNENs) in order to reveal the associations between morphological and molecular parameters. The local tumour spread (T), presence of metastases in regional lymph nodes (N) and distant organs (M), tumour grade (G) and resection line status (R) by pathology findings (pTNMGR), mitotic activity, perineural, vascular and lymphatic invasion were assessed in 16 surgically resected PNENs. By immunohistochemistry, expression of Ki-67, p53, p27, p21, cyclin D1, Bcl-2, E-cadherin, CD44, vimentin, cyclooxygenase 2 (COX-2), microvascular density, and cytokeratin (CK) spectrum, along with neuroendocrine, intestinal and squamous markers were detected. Descriptive statistics, Chi-square test, Spearman's rank correlation, Mann-Whitney and Kruskal-Wallis methods were applied; p < 0.05 was considered significant. Ki-67, CK19, p63, vimentin and COX-2 were significantly up-regulated in PNENs in comparison to benign pancreatic islets. A complex network of morphological and molecular associations was identified. Ki-67 correlated with PNEN size (p = 0.022), the World Health Organization 2004 and 2010 classification grades (p = 0.021 and p = 0.002), stage (p = 0.028) and mitotic count (p = 0.007) but among molecular markers -with CK19 (p = 0.033) and vimentin (p = 0.045). CK19 was significantly up-regulated in PNENs, having higher pT (p = 0.018), pR (p = 0.025), vascular (p = 0.020), perineural (p = 0.026) and lymphatic invasion (p = 0.043). In conclusion, proliferation activity (by Ki-67), E-cadherin, vimentin and CK19 are important molecular characteristics of PNENs due to significant associations with morphological tumour characteristics, pTNMGR and invasive growth.

show abstract

“…To our knowledge, there is only one previous study that has examined the relationship between both EGFR and COX-2 tumor expression and survival among pancreatic cancer patients in the same study. Lozano-Leon and colleagues (41) reported no significant associations between EGFR or COX-2 expression and survival. In contrast to our study, where we used whole tissue sections, they performed IHC on tissue microarrays, which may have its limitations in survival analysis in small patient materials and when the number of tumor cores is limited (42).…”

Section: Discussionmentioning

confidence: 99%

EGFR, but not COX‑2, protein in resected pancreatic ductal adenocarcinoma is associated with poor survival

et al. 2019

View full text Add to dashboard Cite

The effects of EGFR and COX-2 protein overexpression on clinical outcomes in pancreatic ductal adenocarcinoma (PDAC) patients remains unclear. Therefore, the aim of the present study was to evaluate the protein expression of epithelial growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in tumor cells in surgically resected PDAC, in comparison with clinicopathological characteristics and clinical outcomes. Immunohistochemical staining of formalin-fixed paraffin-embedded tissue derived from surgically resected tumors was performed. Tissue slides were evaluated for membrane wild-type EGFR and cytoplasmic COX-2 staining using a histoscore system. Statistical associations between EGFR and COX-2 staining and clinicopathological characteristics were examined to predict survival. In a cohort of 32 resected PDAC patients, high EGFR protein expression in tumor cells was significantly associated with shorter median overall survival (7.9 vs. 39.2 months, P=0.0038). The corresponding hazard ratio (HR) for patients with high EGFR protein expression in tumor cells was 3.12 [95% confidence interval (CI): 1.39–7.00, P=0.006]. COX-2 protein expression was not associated with survival (22.6 vs. 24.5 months P=0.60; HR 1.22 95% CI: 0.59–2.51, P=0.60). Following multivariate Cox regression analysis, high EGFR protein expression in tumor cells (P=0.043) remained as significant independent prognostic factor for survival. In conclusion, high wild-type EGFR protein expression, but not COX-2 protein expression, in tumor cells is a prognostic factor for reduced overall survival following pancreatic tumor resection, supporting a role for EGFR in identifying resected patients that may benefit from EGFR-targeted therapy.

show abstract

Ductal adenocarcinoma of the pancreas: Expression of growth factor receptors, oncogenes and suppressor genes, and their relationship to pathological features, staging and survival

Cited by 14 publications

References 33 publications

Enhancing efficacy of gemcitabine in pancreatic patient-derived xenograft mouse models

Enhancing efficacy of gemcitabine in pancreatic patient-derived xenograft mouse models

Original paper Morphological and immunohistochemical profile of pancreatic neuroendocrine neoplasms

EGFR, but not COX‑2, protein in resected pancreatic ductal adenocarcinoma is associated with poor survival

Contact Info

Product

Resources

About