Genetic Tumor Markers With Prognostic Impact in Dukes’ Stages B and C Colorectal Cancer Patients

Diep, Chieu B.; Thorstensen, Lin; Meling, Gunn Iren; Skovlund, Eva; Rognum, Torleiv O.; Lothe, Ragnhild

doi:10.1200/jco.2003.05.190

Cited by 125 publications

(78 citation statements)

References 73 publications

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“…There have been several attempts to identify this subset of patients both at histopathological and more often at molecular levels. At the genomic level, few studies have focused on early-stage colorectal cancer [3][4][5][6] and of those studies that focused on early-stage colorectal cancer, the analysis was limited to few chromosomes. 7,8 Therefore, there is currently a need to profile primary tumours from early-stage colorectal cancer using genome-wide scanning techniques that can also be integrated into current laboratory practices.…”

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confidence: 99%

Genetic profiling of stage I and II colorectal cancer may predict metastatic relapse

et al. 2006

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A substantial number of patients with early-stage colorectal cancer relapse from metastatic disease. Identification of these patients by genetic profiling of their primary tumours may allow more informed followup and tailored administration of adjuvant therapy. Primary tumours from 70 patients with early-stage and largely microsatellite-stable colorectal cancer were profiled using metaphase-based comparative genomic hybridization (CGH) and the aberrations confirmed independently in a subset of patients using microarraybased CGH. Of the 70 cancers, 61 were amenable to CGH, and follow-up data was available from 56 patients. Genomic aberrations were correlated with patients' survival using univariate, multivariate and Kaplan-Meier survival curves. Metastatic primary tumours exhibited more complex genomic aberrations than non-metastatic primary tumours. Loss of chromosome 4p was an independent prognostic factor in early-stage colorectal cancer using multivariate analysis (Hazard ratio, 9.6; 95% CI, 3.3-28; P ¼ 0.0001). Loss of both chromosome arms 8p and 18q had a statistically significant negative effect on disease-free survival. Moreover, primary tumours with loss of both chromosomes 4 and 14q bestowed poorer prognosis than tumours with loss of any one of the two chromosomes (Po0.0001). Genetic profiling of primary tumours of patients with early-stage colorectal cancer is of significant value in identifying the subset of patients who may relapse with metastatic disease. Accordingly, the molecular genetic features of primary tumours should be considered in the mainstream management of patients with this specific stage of the disease.

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confidence: 99%

Genetic profiling of stage I and II colorectal cancer may predict metastatic relapse

et al. 2006

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“…However, the prognostic role of TP53-inactivating mutations is still in question (Iacopetta et al, 2006). Similarly, the impacts of epidermal growth factor receptor (EGFR) over-expression, loss of heterozygosity in chromosome 18q, somatic adenomatous polyposis coli (APC), and KRAS mutations on survival remain unclear (Diep et al, 2003;Spano et al, 2005;Walther et al, 2009).…”

Section: Molecular Markersmentioning

confidence: 99%

“…In these cases, inactivating mutations (29% of all CRCs) are correlated with advanced stage and vascular and lymphatic involvement. Diep et al (2003) showed that TP53 mutations affecting the L3 zinc-binding domain and lower survival rate in the subclassification of Dukes' B and C patients and may have an impact on the ideal treatment strategy. However, the prognostic role of TP53-inactivating mutations is still in question (Iacopetta et al, 2006).…”

Section: Molecular Markersmentioning

confidence: 99%

Molecular biomarkers of colorectal cancer: prognostic and predictive tools for clinical practice

Jiang

et al. 2012

J. Zhejiang Univ. Sci. B

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Abstract:Colorectal cancer remains one of the most common types of cancer and leading causes of cancer death worldwide. Although we have made steady progress in chemotherapy and targeted therapy, evidence suggests that the majority of patients undergoing drug therapy experience severe, debilitating, and even lethal adverse drug events which considerably outweigh the benefits. The identification of suitable biomarkers will allow clinicians to deliver the most appropriate drugs to specific patients and spare them ineffective and expensive treatments. Prognostic and predictive biomarkers have been the subjects of many published papers, but few have been widely incorporated into clinical practice. Here, we want to review recent biomarker data related to colorectal cancer, which may have been ready for clinical use.

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“…Allelic imbalances (AIs) appearing as loss of heterozygosity (LOH) or as microsatellite instability (MSI) have been detected in the circulating DNA of patients with a variety of malignancies, such as non-small-cell lung cancer (Sozzi et al, 1999), renal cell carcinoma (Gonzalgo et al, 2002), bladder cancer (Utting et al, 2002), breast cancer (Silva et al, 1999), colon cancer (Diep et al, 2003), and malignant melanoma (Taback et al, 2004). Nawroz et al (1996) first demonstrated that AIs could be detected in the plasma/ serum DNA of head and neck SCC, suggesting that circulating tumour-associated DNA in the blood of patients with oral SCC can be a key determinant in predicting tumour recurrences or metastasis.…”

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confidence: 99%

Monitoring of circulating tumour-associated DNA as a prognostic tool for oral squamous cell carcinoma

et al. 2005

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Frequent allelic imbalances (AIs) including loss of heterozygosity and microsatellite instability on a specific chromosomal region have been identified in a variety of human malignancies. The objective of our study was to assess the possibility of prognostication and monitoring of oral squamous cell carcinoma (SCC) by microsatellite blood assay. DNA from normal and tumorous tissues and serum DNA obtained at three time points (preoperatively, postoperatively, and 4 weeks postoperatively) from 64 patients with oral SCC was examined at nine microsatellite loci. In all, 38 (59%) DNA samples from tumorous tissues and 52% from serum showed AIs in at least one locus. Patterns of AIs in the serum DNA were matched to those detected in tumour DNA. Of them, AIs were frequently detected preoperatively (44%, 28 of 64), and postoperatively (20%, 13 of 64). Moreover, among 12 cases with AIs during the postoperative period, six had no evidence of an AI 4 weeks postoperatively, and they had no recurrence and were disease free. In contrast, six patients with AI-positive DNA 4 weeks postoperatively have died with distant metastasis within 44 weeks. Thus, our results suggest that the assessment of microsatellite status in the serum DNA could be a useful predictive tool to monitor disease prognosis.

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Genetic Tumor Markers With Prognostic Impact in Dukes’ Stages B and C Colorectal Cancer Patients

Abstract: The present study indicates that 17p, 18q, and 20q genotypes, and TP53 mutation status add information in the subclassification of Dukes' B and C patients and may have impact on the choice of treatment.

Cited by 125 publications

References 73 publications

Genetic profiling of stage I and II colorectal cancer may predict metastatic relapse

Genetic profiling of stage I and II colorectal cancer may predict metastatic relapse

Molecular biomarkers of colorectal cancer: prognostic and predictive tools for clinical practice

Monitoring of circulating tumour-associated DNA as a prognostic tool for oral squamous cell carcinoma

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