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Tumor budding cells, cancer stem cells and epithelial-mesenchymal transition-type cells in pancreatic cancer.

Karamitopoulou E - Front Oncol (2013)

Bottom Line: Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4) and dysregulation of PTEN/PI3K/AKT signaling.Through their interaction with Wingless-INT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial-mesenchymal transition (EMT).Emerging evidence has demonstrated that cancer stem cells (CSCs), small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion, and metastasis in pancreatic cancer.

View Article: PubMed Central - PubMed

Affiliation: Clinical Pathology Division, Institute of Pathology, University of Bern Bern, Switzerland.

ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with a 5-year survival rate of less than 5%. Moreover, PDAC escapes early detection and resists treatment. Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4) and dysregulation of PTEN/PI3K/AKT signaling. Through their interaction with Wingless-INT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial-mesenchymal transition (EMT). Emerging evidence has demonstrated that cancer stem cells (CSCs), small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion, and metastasis in pancreatic cancer. EMT may be histologically represented by the presence of tumor budding which is described as the occurrence of single tumor cells or small clusters (<5) of dedifferentiated cells at the invasive front of gastrointestinal (including colorectal, oesophageal, gastric, and ampullary) carcinomas and is linked to poor prognosis. Tumor budding has recently been shown to occur frequently in PDAC and to be associated with adverse clinicopathological features and decreased disease-free and overall survival. The aim of this review is to present a short overview on the morphological and molecular aspects that underline the relationship between tumor budding cells, CSCs, and EMT-type cells in PDAC.

No MeSH data available.


Related in: MedlinePlus

Low- (A) and high-grade (B) tumor budding in PDAC (pancytokeratin staining, ×400). Arrows indicate examples of tumor budding.
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Figure 1: Low- (A) and high-grade (B) tumor budding in PDAC (pancytokeratin staining, ×400). Arrows indicate examples of tumor budding.

Mentions: In a recent study by our own group the presence and prognostic significance of tumor budding in PDAC were investigated (Karamitopoulou et al., 2012). We found an association between high-grade budding and aggressive clinicopathological features of the tumors, like advanced pT-stage and the presence of lymphatic invasion. Furthermore, we could show that tumor budding occurs frequently in pancreatic cancer and is a strong and independent prognostic factor that can be used as an indicator of patient outcome having a more powerful prognostic ability than other more classic prognostic factors including TNM (Tumor, Node, Metastasis) stage. In more detail, high-grade tumor budding was strongly associated with less overall and disease-free survival, while patients with low-grade budding survived longer and had longer disease-free intervals independently of the presence of other adverse prognostic factors like lymphatic invasion, presence of lymph node metastasis or positive resection margins (Figures 1A,B).


Tumor budding cells, cancer stem cells and epithelial-mesenchymal transition-type cells in pancreatic cancer.

Karamitopoulou E - Front Oncol (2013)

Low- (A) and high-grade (B) tumor budding in PDAC (pancytokeratin staining, ×400). Arrows indicate examples of tumor budding.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539658&req=5

Figure 1: Low- (A) and high-grade (B) tumor budding in PDAC (pancytokeratin staining, ×400). Arrows indicate examples of tumor budding.
Mentions: In a recent study by our own group the presence and prognostic significance of tumor budding in PDAC were investigated (Karamitopoulou et al., 2012). We found an association between high-grade budding and aggressive clinicopathological features of the tumors, like advanced pT-stage and the presence of lymphatic invasion. Furthermore, we could show that tumor budding occurs frequently in pancreatic cancer and is a strong and independent prognostic factor that can be used as an indicator of patient outcome having a more powerful prognostic ability than other more classic prognostic factors including TNM (Tumor, Node, Metastasis) stage. In more detail, high-grade tumor budding was strongly associated with less overall and disease-free survival, while patients with low-grade budding survived longer and had longer disease-free intervals independently of the presence of other adverse prognostic factors like lymphatic invasion, presence of lymph node metastasis or positive resection margins (Figures 1A,B).

Bottom Line: Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4) and dysregulation of PTEN/PI3K/AKT signaling.Through their interaction with Wingless-INT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial-mesenchymal transition (EMT).Emerging evidence has demonstrated that cancer stem cells (CSCs), small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion, and metastasis in pancreatic cancer.

View Article: PubMed Central - PubMed

Affiliation: Clinical Pathology Division, Institute of Pathology, University of Bern Bern, Switzerland.

ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with a 5-year survival rate of less than 5%. Moreover, PDAC escapes early detection and resists treatment. Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4) and dysregulation of PTEN/PI3K/AKT signaling. Through their interaction with Wingless-INT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial-mesenchymal transition (EMT). Emerging evidence has demonstrated that cancer stem cells (CSCs), small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion, and metastasis in pancreatic cancer. EMT may be histologically represented by the presence of tumor budding which is described as the occurrence of single tumor cells or small clusters (<5) of dedifferentiated cells at the invasive front of gastrointestinal (including colorectal, oesophageal, gastric, and ampullary) carcinomas and is linked to poor prognosis. Tumor budding has recently been shown to occur frequently in PDAC and to be associated with adverse clinicopathological features and decreased disease-free and overall survival. The aim of this review is to present a short overview on the morphological and molecular aspects that underline the relationship between tumor budding cells, CSCs, and EMT-type cells in PDAC.

No MeSH data available.


Related in: MedlinePlus