Patient and Tumor Characteristics and BRAF and KRAS Mutations in Colon Cancer, NCCTG/Alliance N0147

Abstract Background: Tumor budding is now emerging as one of the robust and promising histological factors that play an important role in colon cancer. In this study, we aimed to investigate the association between tumor budding and tumor clinicopathological factors, tumor molecular signature, and patient survival for the first time in the Moroccan population. Methods: We collected data of 100 patients with operated colon adenocarcinoma. Tumor budding was assessed on HES slides, according to the International Tumor Budding Consensus Conference 2016 recommendations. The expression of MMR proteins was performed by Immunohistochemistry. KRAS and NRAS mutations testing was performed by Sanger sequencing and pyrosequençing. Results: High tumor budding grade (BUD 3) was found to be significantly associated with adverse clinicopathological features including older age (P=0.03), presence of perineural invasion (P=0.02), presence of vascular invasion (P=0.05), distant metastases (P˂0.001), advanced TNM stage (P=0.001), the occurrence of relapse (P=0.04), and the high number of deceased cases (P=0.02). Interestingly, we found that tumors with high budding were more likely to be microsatellite stable (MSS) (P=0.005) and harbor more KRAS mutations (P=0.02). In all stages, High tumor budding was correlated with poorer overall survival (P=0.04) and decreased relapse-free survival with a difference close to significance ((P=0.09). we concluded that high tumor budding was strongly associated with unfavorable clinicopathological features and special molecular biomarkers and effectively affects the overall survival of CC patients. Conclusions: Based on these findings and the ITBCC group recommendations, tumor budding should be taken into account along with other clinicopathologic factors in the risk assessment of colorectal cancer.

Download Full-text

Comparative study of preoperative prediction scores for lymph node metastasis in gastric and colon cancer patients

10.21203/rs.3.rs-37182/v2 ◽

2020 ◽

Author(s):

Xiangjian Zheng ◽

Xiaodong Chen ◽

Min Li ◽

Chunmeng Li ◽

Xian Shen

Keyword(s):

Risk Factors ◽

Colon Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Cancer Patients ◽

Serum Markers ◽

Tumor Characteristics ◽

Node Metastasis ◽

Preoperative Prediction ◽

Independent Risk Factors

Abstract Background: Surgery combined with chemo-radiotherapy is a recognized model for the treatment of gastric and colon cancers. Lymph node metastasis determines the patient's surgical or comprehensive treatment plan. This analytical study aims to compare preoperative prediction scores to better predict lymph node metastasis in gastric and colon cancer patients.Methods: This study comprised 768 patients, which included 312 patients with gastric cancer and 462 with colon cancer. Preoperative clinical tumor characteristics, serum markers, and immune indices were evaluated using single-factor analysis. Logistic analysis was designed to recognize independent predictors of lymph node metastasis in these patients. The independent risk factors were integrated into preoperative prediction scores, which were accurately assessed using receiver operating characteristic (ROC) curves.Results: Results showed that serum markers (CA125, hemoglobin, albumin), immune indices (S100, CD31, d2–40), and tumor characteristics (pathological type, size) were independent risk factors for lymph node metastasis in patients with gastric and colon cancer. The preoperative prediction scores reliably predicted lymph node metastasis in gastric and colon cancer patients with a higher area under the ROC curve (0.901). The area was 0.923 and 0.870 in gastric cancer and colon cancer, respectively. Based on the ROC curve, the ideal cutoff value of preoperative prediction scores to predict lymph node metastasis was established to be 287. Conclusion: The preoperative prediction scores is a useful indicator that can be applied to predict lymph node metastasis in gastric and colon cancer patients.

Download Full-text

Elderly patients with colon cancer have unique tumor characteristics and poor survival

Cancer ◽

10.1002/cncr.27753 ◽

2012 ◽

Vol 119 (4) ◽

pp. 739-747 ◽

Cited By ~ 28

Author(s):

Supriya S. Patel ◽

Rebecca Nelson ◽

Julian Sanchez ◽

Wendy Lee ◽

Lori Uyeno ◽

...

Keyword(s):

Colon Cancer ◽

Elderly Patients ◽

Tumor Characteristics ◽

Poor Survival

Download Full-text

Using Naïve Bayesian Analysis to Determine Imaging Characteristics of KRAS Mutations in Metastatic Colon Cancer

Diagnostics ◽

10.3390/diagnostics7030050 ◽

2017 ◽

Vol 7 (3) ◽

pp. 50 ◽

Cited By ~ 4

Author(s):

Yash Pershad ◽

Siddharth Govindan ◽

Amy Hara ◽

Mitesh Borad ◽

Tanios Bekaii-Saab ◽

...

Keyword(s):

Colon Cancer ◽

Bayesian Analysis ◽

Metastatic Colon Cancer ◽

Kras Mutations ◽

Naive Bayesian ◽

Naïve Bayesian ◽

Imaging Characteristics

Download Full-text

Liquid biopsy in colon cancer: comparison of different circulating DNA extraction systems following absolute quantification of KRAS mutations using Intplex allele-specific PCR

Oncotarget ◽

10.18632/oncotarget.21134 ◽

2017 ◽

Vol 8 (49) ◽

pp. 86253-86263 ◽

Cited By ~ 33

Author(s):

Vera Kloten ◽

Nadine Rüchel ◽

Nadina Ortiz Brüchle ◽

Janina Gasthaus ◽

Nils Freudenmacher ◽

...

Keyword(s):

Colon Cancer ◽

Dna Extraction ◽

Liquid Biopsy ◽

Absolute Quantification ◽

Circulating Dna ◽

Kras Mutations ◽

Specific Pcr ◽

Allele Specific ◽

Allele Specific Pcr

Download Full-text

Association of microsatellite instability with distinct clinical and molecular characteristics in resected colon cancer: Analysis of a platform trial of the AIO colorectal study group—Colopredict Plus.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15086 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15086-e15086

Author(s):

Anke C. Reinacher-Schick ◽

Hendrik Juette ◽

Stefanie Noepel-Duennebacke ◽

Dirk Arnold ◽

Nadezda Basara ◽

...

Keyword(s):

Colon Cancer ◽

Molecular Markers ◽

Microsatellite Instability ◽

Real Life ◽

Stage Ii ◽

Molecular Characteristics ◽

Braf Mutations ◽

Kras Mutations ◽

Primary Tumor Site ◽

Reported Data

e15086 Background: High microsatellite instability (MSI-H) is a prognostic marker in resected colon cancer (CC) identified in post-hoc analysis of multiple trials. However, validation in real-life cohorts and its association with clinical and molecular markers is lacking. Methods: In Sep 2013 we started a platform trial in 49 German cancer centers recruiting patients with UICC stage II and III CC diagnosed between 2008 to 2016. MSI was tested by immunohistochemistry (IHC) of mismatch repair proteins MLH1, MSH2, MSH6 and PMS2. In case of any loss of protein expression (IHC neg), fragment length analysis (FLA) was performed, defining MSI high tumors (MSI-H) and MS stable tumors (MSS). Besides, mutations in known prognostic factors for CC such as RAS, BRAF, PI3K and others were determined by next generation sequencing (NGS). Results: By end of 2016, 1249 patients have been recruited into the trial: median age 73yrs., stage II/III: 686/563 pts. So far, tissue was analysed in 512 pts. Of these, 182 pts. were IHC neg with 116 pts. tested MSI-H upon FLA (22.7%). Median age was 73yrs., female/male: 260/252 pts., stageII/III: 292/220 pts. Association of MS status with clinical factors is shown in Table 1. Upon NGS analysis we found 16.3% BRAF mutations, 39% KRAS mutations, 2.8% NRAS mutations and 22.6% PI3K mutations. MSI-H status was significantly associated with BRAF mutation and wildtype status of RAS. Conclusions: We found a higher percentage of MSI-H cancers in our registry compared to reported data from randomised trials, possibly related to a higher median age in this real-life cohort. MSI-H was associated with female sex, primary tumor site, and distinct molecular markers and should therefore be considered a heterogeneous subgroup of CC. Updated analysis including NGS data and survival will be presented at the meeting. Clinical trial information: AIO- KRK-0413, DKRS:00004305. [Table: see text]

Download Full-text

Effect of panitumumab on autophagy in colon cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e22151 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e22151-e22151

Author(s):

H. P. Kalofonos ◽

A. Antonacopoulou ◽

P. Matsouka ◽

E. Giannopoulou

Keyword(s):

Cell Cycle ◽

Colon Cancer ◽

Cell Proliferation ◽

Redox Status ◽

Colon Cancer Cell ◽

Wild Type ◽

Kras Mutations ◽

Protein Levels ◽

Cycle Arrest ◽

Ht 29

e22151 Background: Panitumumab, a human monoclonal antibody raised against EGFR, has been approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) for the treatment of patients with EGFR-expressing mCRC and wild type kras. The ratio of reduced/oxidised form of glutathione (GSH/GSSG) is an indicator of the redox status in cells. The aim of the current study was to investigate the effect of panitumumab on the redox status of colon cancer cell lines Caco-2, DLD-1 and HT-29 regarding proliferation, apoptosis, necrosis, cell cycle arrest and autophagy. Methods: Cell proliferation was measured by MTT assay. Apoptosis and necrosis were detected by annexin v/propidium iodide assay. Cell cycle arrest was estimated by propidium iodide assay. Autophagy was detected by immunobloting and GSH levels were measured by spectrophotometrical analysis. kras mutations were detected by sequencing analysis. Results: Caco-2, DLD-1 and HT-29 cell lines differ in the expression levels of EGFR and HER-2. Kras mutation analysis in previous studies and in the current study showed that DLD-1 cells express mutated kras while Caco-2 and HT-29 cells express wild type of kras. Panitumumab decreased proliferation only in DLD-1 cells 48 h after its application besides the mutated kras. However, panitumumab did not affect DLD-1 cell apoptosis, necrosis or cell cycle progression 24 and 48 h after cells treatment. Interestingly, panitumumab increased protein levels of beclin 1, an indicator of autophagy, 24 h after its addition in cells. Moreover, an increase in GSH levels was noted 48 h after cells treatment with panitumumab. Conclusions: This is the first study to show that panitumumab, an EGFR inhibitor, affects colon cancer cell proliferation independently of kras mutations and EGFR protein levels through the induction of autophagy. The inhibition in cell proliferation was followed by an increase in GSH levels reflecting an imbalance on the redox status of cells. No significant financial relationships to disclose.

Download Full-text