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.

KRAS mutation as a predictor for cause-specific survival in early- versus late-onset colorectal cancer: A United States population-based study.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 580-580
Author(s):  
Albert Y. Lin ◽  
Amanda R Kahl ◽  
Jennifer Y. Pan ◽  
Joshua Lo ◽  
Winifred Tung ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Kras Mutation ◽  
Late Onset ◽  
Incidence Rates ◽  
Cox Proportional Hazards ◽  
Kras Mutations ◽  
Poor Prognostic Factor ◽  
Rectal Cancers ◽  
Cause Specific Survival

580 Background: While the overall incidence rates for colorectal cancer (CRC) —the third leading cancer diagnosis in the U.S.—have been decreasing over the last several decades, incidence rates for early-onset (EO, age 20-49 years) CRC have shown an upward trend. Multiple studies have documented mutations in KRAS proto-oncogene (KRAS) as a poor prognostic factor in sporadic CRC, but its impact on EO versus late-onset (LO, age > 49 years) CRC is unclear. Methods: Surveillance, Epidemiology, and End Results (SEER) Program data were queried to identify pathologically-confirmed CRC cases tested for KRAS and diagnosed between 2010 and 2015. Demographic, histologic, and KRAS data were compared between EO and LO using Chi-square tests. Kaplan-Meier and Cox proportional hazards models were used to estimate cause-specific survival (CSS) and examine factors associated with CSS. Results: Of 202,173 CRC cases, 3,842 EO and 17,819 LO CRC cases had KRAS testing with a KRAS mutation frequency of 40% and 41%, respectively. Compared with LO tumors harboring mutated KRAS, EO tumors with KRAS mutations were more frequently found in females (52% vs. 45%, P < 0.001), left-sided (LS) or rectal cancers (62% vs. 48%, P < 0.001), stage III/IV (89% vs. 81%, P < 0.001), and grade III/IV (21% vs. 18%, P = 0.038). Compared to CSS in EO with KRAS mutation, LO with KRAS mutation was associated with worse prognosis—with an overall hazard ratio (HR) of 1.21 (95% CI, 1.15-1.27, P < 0.0001). Results [HR (95% CI)] from Cox analyses on the effects of KRAS mutation on CSS, stratified by sidedness, are shown below. Conclusions: Despite EO CRC carrying worse prognostic factors than LO CRC, it confers better CSS than LO CRC. EO CRC is distinct from LO CRC in clinical and pathological features, in addition to its response to mutant KRAS. Mutated KRAS is an independent prognostic factor in LS colon and rectal cancers among the LO, but not in the EO population. [Table: see text]

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.

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