The Prognostic Value of Microsatellite Instability, KRAS, BRAF and PIK3CA Mutations in Stage II Colon Cancer Patients

e15075 Background: The prognostic role of microsatellite instability (MSI) in stage II colon cancer patients remains controversial despite it has been investigated in a number of studies. Hazard ratios differ considerably among these studies. We performed a meta-analysis to define the significance of MSI in this group of patients. Methods: Studies indexed in PubMed presenting separate data on MSI status and survival outcomes for stage II colon cancer patients have been analyzed using fixed-effect meta-analysis of hazard ratio according to the method of Peto. Results: Analysis was performed on 19 studies including 5998 patients. 47.2% patients received postoperative chemotherapy, 52.8% were males and 47.2% females. Eight studies included also rectal cancer patients. MSI was detected in 20.8 % of the patients. Hazard ration (HR) for overall survival (OS): MSI vs MSS for the entire population: 0.73 (95% confidence interval (CI): 0.33-1.65); HR for disease free survival (DFS): 0.60 (95% CI: 0.27-1.32). No statistical significant difference was found when comparing studies analyzing MSI with genotyping (MG) and immunohistochemistry (IHC) (MG vs IHC: HR OS 0.45, 95% CI 0.10-2.05 vs. 0.95, 95% CI 0.57–1.58; HR DFS 0.51, 95% CI: 0.14-1.85 vs. 0.67, 95% CI 0.26-1.70). However, numerically MSI determination with genotyping shows remarkably lower hazard ratios (further from HR equal to one) for both OS and DFS. Separate analysis of studies investigating colon cancer patients only showed HR OS 0.72 (95% CI: 0.31-1.71); HR DFS 0.60 (95% CI: 0.27-1.31). Conclusions: This is the first meta-analysis that evaluates the prognostic role of MSI in the well defined population of colon cancer patients with stage II disease. No significant relation was found between MSI status and various survival outcomes. Routine determination of MSI status to guide postoperative management of stage II colon cancer patients cannot be recommended based on the presently included studies. This study was supported from the unrestricted grant of Cancerforskningsfonden i Norrland/Lions Cancerforskningsfond LP 14-2065 and Akademisk Miljö NLL-576531.

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Prognostic value of nucleotyping, DNA ploidy and stroma in high-risk stage II colon cancer

British Journal of Cancer ◽

10.1038/s41416-020-0974-8 ◽

2020 ◽

Vol 123 (6) ◽

pp. 973-981 ◽

Cited By ~ 1

Author(s):

Lujing Yang ◽

Pengju Chen ◽

Li Zhang ◽

Lin Wang ◽

Tingting Sun ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Cancer Patients ◽

Prognostic Value ◽

Dna Ploidy ◽

Univariate Analysis ◽

Disease Free Survival ◽

Stage Ii ◽

Contributory Factor ◽

Stage Ii Colon Cancer

Abstract Background Heterogeneity with respect to recurrence and survival in high-risk stage II colon cancer patients still exists, and further classification is urgently required. This study aimed to ascertain the prognostic value of DNA ploidy, stroma-tumour fraction and nucleotyping in the prognosis of high-risk stage II colon cancer. Methods A total of 188 high-risk stage II colon cancer patients received radical surgery in Peking University Cancer Hospital, from 2009 to 2015. Status of mismatch repair proteins in tumours was analysed using immunohistochemistry. DNA ploidy, stroma-tumour fraction and nucleotyping were estimated by automated digital imaging systems. Results Nucleotyping and DNA ploidy were significant prognostic factors, while stroma-tumour fraction were not significantly prognostic in the univariate analysis. In the multivariable model, the dominant contributory factor of disease-free survival was chromatin heterogeneous vs. chromatin homogeneous [HR 3.309 (95% CI: 1.668–6.564), P = 0.001]. Conclusions Our study indicates that nucleotyping is an independent prognostic factor in high-risk stage II colon cancer. Therefore, it may help subdivide patients into different subgroups and give them different strategies for follow-up and treatment in the future.

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Prognostic value of MACC1 and proficient mismatch repair status for recurrence risk prediction in stage II colon cancer patients: the BIOGRID studies

Annals of Oncology ◽

10.1093/annonc/mdx207 ◽

2017 ◽

Vol 28 (8) ◽

pp. 1869-1875 ◽

Cited By ~ 16

Author(s):

U.-P. Rohr ◽

P. Herrmann ◽

K. Ilm ◽

H. Zhang ◽

S. Lohmann ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Patients ◽

Mismatch Repair ◽

Risk Prediction ◽

Prognostic Value ◽

Recurrence Risk ◽

Stage Ii ◽

Mismatch Repair Status ◽

Stage Ii Colon Cancer

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Prognostic value of clinical, pathological and immunohistochemical markers in stage II colon cancer patients

Acta chirurgica iugoslavica ◽

10.2298/aci0803039s ◽

2008 ◽

Vol 55 (3) ◽

pp. 39-44 ◽

Cited By ~ 4

Author(s):

Z. Stor ◽

G.S. Frkovic ◽

M. Bracko ◽

S. Repse

Keyword(s):

Colon Cancer ◽

Molecular Markers ◽

Cancer Patients ◽

Prognostic Value ◽

Perineural Invasion ◽

Histological Grade ◽

Tnm Stage ◽

Stage Ii ◽

Immunohistochemical Markers ◽

Stage Ii Colon Cancer

Background/Aims: The purpose of our analysis was to determine the prognostic value of molecular markers for identifying high-risk TNM stage II colon cancer patients, the association with various clinical and pathological features, and possible relation to survival. Methods: In 191 colon cancer patients who underwent a potentially curative resection, clinical and pathological factors (age, tumour site, histological grade of malignancy, pT stage, presence of venous, lymphatic and perineural invasion) and tumour molecular markers were analyzed. Molecular markers were assessed immunohistochemically in sections of paraffin- embedded tissues. Patients were followed for a median of 8.7 years. The 5-year survival rate was estimated using the Kaplan-Meier statistical method. Results: From 1. Jan.1994 to 31.Dec.2000, 191 patients underwent radical resection for T3-4 N0M0 colorectal cancer without adjuvant chemotherapy. A significant decrease in survival was identified in older patients, patients with tumours pT4 and with perineural invasion. We found no significant differences in survival of patients with expression of MLH1, Cyclin D1 and reduced overexpression of E-cadherin. Conclusions: The results of our study indicate that the presence of perineural invasion, pT4 stage and the patient?s age are significantly correlated with the expected survival in radically resected TNM stage II colon cancer patients, while immunohistochemical markers are not related to survival.

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Microsatellite Instability as a Prognostic Factor in Stage II Colon Cancer Patients, a Meta-Analysis of Published Literature

Anticancer Research ◽

10.21873/anticanres.12113 ◽

2017 ◽

Vol 37 (12) ◽

Cited By ~ 2

Keyword(s):

Colon Cancer ◽

Prognostic Factor ◽

Microsatellite Instability ◽

Cancer Patients ◽

Meta Analysis ◽

Stage Ii ◽

Stage Ii Colon Cancer

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Prognostic value of desmoplastic reaction characterisation in stage II colon cancer: prospective validation in a Phase 3 study (SACURA Trial)

British Journal of Cancer ◽

10.1038/s41416-020-01222-8 ◽

2021 ◽

Author(s):

Hideki Ueno ◽

Megumi Ishiguro ◽

Eiji Nakatani ◽

Toshiaki Ishikawa ◽

Hiroyuki Uetake ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Patients ◽

Prognostic Value ◽

Cox Model ◽

Conditional Inference ◽

Stage Ii ◽

Controlled Study ◽

Prognostic Information ◽

Desmoplastic Reaction ◽

Stage Ii Colon Cancer

Abstract Background The characterisation of desmoplastic reaction (DR) has emerged as a new, independent prognostic determinant in colorectal cancer. Herein, we report the validation of its prognostic value in a randomised controlled study (SACURA trial). Methods The study included 991 stage II colon cancer patients. DR was classified by the central review as Mature, Intermediate or Immature based on the presence of hyalinised collagen bundles and myxoid stroma at the desmoplastic front. All clinical and pathological data, including DR characterisations, were prospectively recorded and analysed 5 years after the completion of the registration. Results The five-year relapse-free survival (RFS) rate was the highest in the Mature group (N = 638), followed by the Intermediate (N = 294) and Immature groups (N = 59). Multivariate analysis revealed that DR classification was an independent prognostic factor, and based on Harrell’s C-index, the Cox model for predicting RFS was significantly improved by including DR. In the conditional inference tree analysis, DR categorisation was the first split factor for predicting RFS, followed by T-stage, microsatellite instability status and budding. Conclusions Histological categorisation of DR provides important prognostic information that could contribute to the efficient selection of stage II colon cancer patients who would benefit from postoperative adjuvant therapy.

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Association of chemotherapy with survival in stage II colon cancer patients who received radical surgery: a retrospective cohort study

BMC Cancer ◽

10.1186/s12885-021-08057-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhihao Lv ◽

Yuqi Liang ◽

Huaxi Liu ◽

Delong Mo

Keyword(s):

Colon Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Prediction Models ◽

Radical Surgery ◽

Survival Rates ◽

Stage Ii ◽

Survival Prediction ◽

Stage Ii Colon Cancer ◽

Overall Survival Rates

Abstract Background It remains controversial whether patients with Stage II colon cancer would benefit from chemotherapy after radical surgery. This study aims to assess the real effectiveness of chemotherapy in patients with stage II colon cancer undergoing radical surgery and to construct survival prediction models to predict the survival benefits of chemotherapy. Methods Data for stage II colon cancer patients with radical surgery were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (1:1) was performed according to receive or not receive chemotherapy. Competitive risk regression models were used to assess colon cancer cause-specific death (CSD) and non-colon cancer cause-specific death (NCSD). Survival prediction nomograms were constructed to predict overall survival (OS) and colon cancer cause-specific survival (CSS). The predictive abilities of the constructed models were evaluated by the concordance indexes (C-indexes) and calibration curves. Results A total of 25,110 patients were identified, 21.7% received chemotherapy, and 78.3% were without chemotherapy. A total of 10,916 patients were extracted after propensity score matching. The estimated 3-year overall survival rates of chemotherapy were 0.7% higher than non- chemotherapy. The estimated 5-year and 10-year overall survival rates of non-chemotherapy were 1.3 and 2.1% higher than chemotherapy, respectively. Survival prediction models showed good discrimination (the C-indexes between 0.582 and 0.757) and excellent calibration. Conclusions Chemotherapy improves the short-term (43 months) survival benefit of stage II colon cancer patients who received radical surgery. Survival prediction models can be used to predict OS and CSS of patients receiving chemotherapy as well as OS and CSS of patients not receiving chemotherapy and to make individualized treatment recommendations for stage II colon cancer patients who received radical surgery.

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