scholarly journals Epithelial mesenchymal transition and tumor budding in aggressive colorectal cancer: Tumor budding as oncotarget

Oncotarget ◽  
2010 ◽  
Vol 1 (7) ◽  
pp. 651-661 ◽  
Author(s):  
Inti Zlobec ◽  
Alessandro Lugli
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Budding ◽  
Mesenchymal Transition ◽  
Cancer Tumor

Combined analysis of tumor budding and tumor microenvironment in patients with stage III colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 652-652
Author(s):  
Hiromichi Nakajima ◽  
Naoko Inoshita ◽  
Chihiro Kondoh ◽  
Yukinori Ozaki ◽  
Kenji Tomizawa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Tumor Microenvironment ◽  
Epithelial Mesenchymal Transition ◽  
Cox Proportional Hazards ◽  
Stage Iii ◽  
Tumor Budding ◽  
Poor Prognostic Factor ◽  
Combined Analysis ◽  
Mesenchymal Transition

652 Background: Tumor budding (TB) represents the epithelial-mesenchymal transition (EMT) and is a novel marker that predicts metastasis and poor survival in patients with colorectal cancer. Although recent preclinical studies have elucidated the interaction between the EMT process and tumor microenvironment (TME), the clinicopathological correlation between TB and TME remains unclear. Methods: Formalin-fixed paraffin-embedded blocks of specimens were obtained from patients with stage III colorectal cancer who underwent surgical resection and adjuvant chemotherapy at our institution between January 2009 and July 2012. TB, tumor stroma percentage (TSP), and inflammatory reaction (IR) graded using the Klintrup-Mäkinen method were evaluated on hematoxylin and eosin sections. The densities of CD8+ T-cells at the tumor centers and invasive margins were analyzed using immunohistochemistry and digital image analysis. Cox proportional hazards models were used to assess the effect of clinicopathological variables on relapse-free survival (RFS). Results: One hundred and ninety-five patients were included in this analysis. The median age was 62 years (range 32–84 years). The median follow-up duration of this study was 5.8 years. High TB ( > 5 buds/0.785 mm2) was observed in 106 patients (54.4%) and was associated with high TSP (P < 0.01), but not with IR and CD8 expression. Multivariate analysis, including clinicopathological factors such as histology, TB, TSP, and IR revealed that high TB was an independent poor prognostic factor (hazard ratio, 1.89; 95% confidence interval, 1.04–3.45; P = 0.04). Patients with high TB and low IR (21.0%) exhibited a shorter survival than others; the 5-year RFS rates were 82.7%, 81.1%, 78.4%, and 40.8% in patients with low TB and high IR, low TB and IR, high TB and high IR, and high TB and low IR, respectively. Conclusions: Our study demonstrated that high TB was an adverse prognostic factor, regardless of TME status. The combined analysis of TB plus IR could improve prognostic value in patients with stage III colorectal cancer. Patients with high TB and low IR may need novel therapeutic approaches.

scholarly journals C4.4A is associated with tumor budding and epithelial-mesenchymal transition of colorectal cancer

2012 ◽  
Vol 103 (6) ◽  
pp. 1155-1164 ◽  
Author(s):  
Ryota Oshiro ◽  
Hirofumi Yamamoto ◽  
Hidekazu Takahashi ◽  
Masahisa Ohtsuka ◽  
Xin Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Budding ◽  
Mesenchymal Transition

scholarly journals Membranous S100A10 Involvement in the Tumor Budding of Colorectal Cancer During Oncogenesis: Report of Two Cases with Immunohistochemical Analysis

2020 ◽  
Author(s):  
Kazumori Arai ◽  
Hisato Ishimatsu ◽  
Tomohiro Iwasaki ◽  
Chinatsu Tsuchiya ◽  
Akihiro Sonoda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
S100 Protein ◽  
Immunohistochemical Analysis ◽  
Tumor Budding ◽  
Plasminogen Activation ◽  
Cell Dynamics ◽  
Regional Lymph Nodes ◽  
Mesenchymal Transition

Abstract Background: Tumor budding (TB) and poorly differentiated clusters (PDCs) are a sequence of histologic findings that predict worse prognosis and node metastasis in colorectal cancer (CRC). TB and PDC (TB/PDC) are caused by cancer cell detachment and are distinguished by the number of cancer cells that constitute a cell cluster. In short, PDC is regarded as the previous step of TB. TB/PDC and epithelial–mesenchymal transition (EMT) are closely linked, but its pathogenic mechanisms are still unclear. S100A10, a member of the S100 protein family, forms a heterocomplex with annexin A2 (ANX A2) and then translocates to cell membrane from the cytoplasm and plays various roles in cell dynamics, including plasminogen activation. S100A10 is the activation modulator of the heterocomplex and promotes cell invasion. S100A10 is involved in the remodeling of both actin and extracellular matrix (ECM), which is also associated with EMT. Case presentation: In two representative cases of conventional advanced CRC, we immunohistochemically examined S100A10 and ANX A2 expressions in which both TB and PDC were prominent. Both CRCs metastasized to multiple regional lymph nodes. In both cases, a membranous positivity for S100A10 was diffusely found in both tumor buds and PDCs and was observed in the tumor cells protruding toward the stroma, giving rise to TB/PDC. However, even in tumor glands with TB/PDC, the tumor cells with a smooth border around the stroma showed either cytoplasmic fine-granular expression or no positivity. The immunoreactivity for ANX A2 was almost the same as that for S100A10. In the main tumor components without TB/PDC, no distinct positivity was detected at their smooth borders. Conclusions: During oncogenesis, membranous S100A10 has the potential to be related to TB of CRC. This may be due to plasminogen activation, actin remodeling, and interaction with an altered ECM. However, further study is required to confirm this hypothesis.

scholarly journals Membranous S100A10 involvement in the tumor budding of colorectal cancer during oncogenesis: report of two cases with immunohistochemical analysis

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Kazumori Arai ◽  
Hisato Ishimatsu ◽  
Tomohiro Iwasaki ◽  
Chinatsu Tsuchiya ◽  
Akihiro Sonoda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
S100 Protein ◽  
Immunohistochemical Analysis ◽  
Tumor Budding ◽  
Plasminogen Activation ◽  
Cell Dynamics ◽  
Regional Lymph Nodes ◽  
Mesenchymal Transition

Abstract Background Tumor budding (TB) and poorly differentiated clusters (PDCs) are a sequence of histologic findings that predict worse prognosis and node metastasis in colorectal cancer (CRC). TB and PDC (TB/PDC) are caused by cancer cell detachment and are distinguished by the number of cancer cells that constitute a cell cluster. In short, PDC is regarded as the previous step of TB. TB/PDC and epithelial-mesenchymal transition (EMT) are closely linked, but its pathogenic mechanisms are still unclear. S100A10, a member of the S100 protein family, forms a heterocomplex with annexin A2 (ANX A2) and then translocates to cell membrane from the cytoplasm and plays various roles in cell dynamics, including plasminogen activation. S100A10 is the activation modulator of the heterocomplex and promotes cell invasion. S100A10 is involved in the remodeling of both actin and extracellular matrix (ECM), which is also associated with EMT. Case presentation In two representative cases of conventional advanced CRC, we immunohistochemically examined S100A10 and ANX A2 expressions in which both TB and PDC were prominent. Both CRCs metastasized to multiple regional lymph nodes. In both cases, a membranous positivity for S100A10 was diffusely found in both tumor buds and PDCs and was observed in the tumor cells protruding toward the stroma, giving rise to TB/PDC. However, even in tumor glands with TB/PDC, the tumor cells with a smooth border around the stroma showed either cytoplasmic fine-granular expression or no positivity. The immunoreactivity for ANX A2 was almost the same as that for S100A10. In the main tumor components without TB/PDC, no distinct positivity was detected at their smooth borders. Conclusions During oncogenesis, membranous S100A10 has the potential to be related to TB of CRC. This may be due to plasminogen activation, actin remodeling, and interaction with an altered ECM. However, further study is required to confirm this hypothesis.

scholarly journals Membranous S100A10 Involvement in the Tumor Budding of Colorectal Cancer During Oncogenesis: Report of Two Cases with Immunohistochemical Analysis

2020 ◽  
Author(s):  
Kazumori Arai ◽  
Hisato Ishimatsu ◽  
Tomohiro Iwasaki ◽  
Chinatsu Tsuchiya ◽  
Akihiro Sonoda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
S100 Protein ◽  
Immunohistochemical Analysis ◽  
Tumor Budding ◽  
Plasminogen Activation ◽  
Cell Dynamics ◽  
Regional Lymph Nodes ◽  
Mesenchymal Transition

Abstract Background Tumor budding (TB) and poorly differentiated clusters (PDCs) are a sequence of histologic findings that predict worse prognosis and node metastasis in colorectal cancer (CRC). TB and PDC (TB/PDC) are caused by cancer cell detachment and are distinguished by the number of cancer cells that constitute a cell cluster. In short, PDC is regarded as the previous step of TB. TB/PDC and epithelial–mesenchymal transition (EMT) are closely linked, but its pathogenic mechanisms are still unclear. S100A10, a member of the S100 protein family, forms a heterocomplex with annexin A2 (ANX A2) and then translocates to cell membrane from the cytoplasm and plays various roles in cell dynamics, including plasminogen activation. S100A10 is the activation modulator of the heterocomplex and promotes cell invasion. S100A10 is involved in the remodeling of both actin and extracellular matrix (ECM), which is also associated with EMT. Recently, the involvement of S100A10 in EMT has been reported. Furthermore, a recent study suggested that S100A10 and ANX A2 are related to the budding of a special type of CRC cells.Case presentation In two representative cases of conventional advanced CRC, we immunohistochemically examined S100A10 and ANX A2 expressions in which both TB and PDC were prominent. Both CRCs metastasized to multiple regional lymph nodes. In both cases, a membranous positivity for S100A10 was diffusely found in both tumor buds and PDCs and was observed in the tumor cells protruding toward the stroma, which originates from TB/PDC. However, even in tumor glands with TB/PDC, the tumor cells with a smooth border around the stroma showed either cytoplasmic fine-granular expression or no positivity. The immunoreactivity for ANX A2 was almost the same as that for S100A10. In the main tumor components without TB/PDC, no distinct positivity was detected at their smooth borders.Conclusions Membranous S100A10 is related to the TB of CRC during oncogenesis. This is possibly due to plasminogen activation, actin remodeling, and interaction with an altered ECM. However, further study is required to confirm this hypothesis.

Tumor budding at the invasive front of colorectal cancer may not be associated with the epithelial-mesenchymal transition

2017 ◽  
Vol 60 ◽  
pp. 151-159 ◽  
Author(s):  
Noriyuki Yamada ◽  
Tamotsu Sugai ◽  
Makoto Eizuka ◽  
Koudai Tsuchida ◽  
Ryo Sugimoto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Budding ◽  
Invasive Front ◽  
Mesenchymal Transition

scholarly journals Epithelial-Mesenchymal Transition and MicroRNAs in Colorectal Cancer Chemoresistance to FOLFOX

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 75
Author(s):  
Paula I. Escalante ◽  
Luis A. Quiñones ◽  
Héctor R. Contreras
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Methylenetetrahydrofolate Reductase ◽  
Epithelial Mesenchymal Transition ◽  
Late Onset ◽  
Dihydropyrimidine Dehydrogenase ◽  
Acquired Resistance ◽  
Potential Effect ◽  
Mesenchymal Transition ◽  
Folfox Chemotherapy

The FOLFOX scheme, based on the association of 5-fluorouracil and oxaliplatin, is the most frequently indicated chemotherapy scheme for patients diagnosed with metastatic colorectal cancer. Nevertheless, development of chemoresistance is one of the major challenges associated with this disease. It has been reported that epithelial-mesenchymal transition (EMT) is implicated in microRNA-driven modulation of tumor cells response to 5-fluorouracil and oxaliplatin. Moreover, from pharmacogenomic research, it is known that overexpression of genes encoding dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), the DNA repair enzymes ERCC1, ERCC2, and XRCC1, and the phase 2 enzyme GSTP1 impair the response to FOLFOX. It has been observed that EMT is associated with overexpression of DPYD, TYMS, ERCC1, and GSTP1. In this review, we investigated the role of miRNAs as EMT promotors in tumor cells, and its potential effect on the upregulation of DPYD, TYMS, MTHFR, ERCC1, ERCC2, XRCC1, and GSTP1 expression, which would lead to resistance of CRC tumor cells to 5-fluorouracil and oxaliplatin. This constitutes a potential mechanism of epigenetic regulation involved in late-onset of acquired resistance in mCRC patients under FOLFOX chemotherapy. Expression of these biomarker microRNAs could serve as tools for personalized medicine, and as potential therapeutic targets in the future.

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