Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update

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Abstract

Biomarkers currently play an important role in the detection and management of patients with several different types of gastrointestinal cancer, especially colorectal, gastric, gastro-oesophageal junction (GOJ) adenocarcinomas and gastrointestinal stromal tumors (GISTs). The aim of this article is to provide updated and evidence-based guidelines for the use of biomarkers in the different gastrointestinal malignancies. Recommended biomarkers for colorectal cancer include an immunochemical-based fecal occult blood test in screening asymptomatic subjects ≥50 years of age for neoplasia, serial CEA levels in postoperative surveillance of stage II and III patients who may be candidates for surgical resection or systemic therapy in the event of distant metastasis occurring, K-RAS mutation status for identifying patients with advanced disease likely to benefit from anti-EGFR therapeutic antibodies and microsatellite instability testing as a first-line screen for subjects with Lynch syndrome. In advanced gastric or GOJ cancers, measurement of HER2 is recommended in selecting patients for treatment with trastuzumab. For patients with suspected GIST, determination of KIT protein should be used as a diagnostic aid, while KIT mutational analysis may be used for treatment planning in patients with diagnosed GISTs.

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Systematic review of microsatellite instability and colorectal cancer prognosis.

S Popat, R. Hübner, R Houlston (2005)

A number of studies have investigated the relationship between microsatellite instability (MSI) and colorectal cancer (CRC) prognosis. Although many have reported a better survival with MSI, estimates of the hazard ratio (HR) among studies differ. To derive a more precise estimate of the prognostic significance of MSI, we have reviewed and pooled data from published studies. Studies stratifying survival in CRC patients by MSI status were eligible for analysis. The principal outcome measure was the HR. Data from eligible studies were pooled using standard techniques. Thirty-two eligible studies reported survival in a total of 7,642 cases, including 1,277 with MSI. There was no evidence of publication bias. The combined HR estimate for overall survival associated with MSI was 0.65 (95% CI, 0.59 to 0.71; heterogeneity P = .16; I(2) = 20%). This benefit was maintained restricting analyses to clinical trial patients (HR = 0.69; 95% CI, 0.56 to 0.85) and patients with locally advanced CRC (HR = 0.67; 95% CI, 0.58 to 0.78). In patients treated with adjuvant fluorouracil (FU) CRCs with MSI had a better prognosis (HR = 0.72; 95% CI, 0.61 to 0.84). However, while data are limited, tumors with MSI derived no benefit from adjuvant FU (HR = 1.24; 95% CI, 0.72 to 2.14). CRCs with MSI have a significantly better prognosis compared to those with intact mismatch repair. Additional studies are needed to further define the benefit of adjuvant chemotherapy in locally advanced tumors with MSI.

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Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer.

Christine Ribic, Daniel Sargent, Malcolm J Moore … (2003)

Colon cancers with high-frequency microsatellite instability have clinical and pathological features that distinguish them from microsatellite-stable tumors. We investigated the usefulness of microsatellite-instability status as a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II and stage III colon cancer. Tumor specimens were collected from patients with colon cancer who were enrolled in randomized trials of fluorouracil-based adjuvant chemotherapy. Microsatellite instability was assessed with the use of mononucleotide and dinucleotide markers. Of 570 tissue specimens, 95 (16.7 percent) exhibited high-frequency microsatellite instability. Among 287 patients who did not receive adjuvant therapy, those with tumors displaying high-frequency microsatellite instability had a better five-year rate of overall survival than patients with tumors exhibiting microsatellite stability or low-frequency instability (hazard ratio for death, 0.31 [95 percent confidence interval, 0.14 to 0.72]; P=0.004). Among patients who received adjuvant chemotherapy, high-frequency microsatellite instability was not correlated with increased overall survival (hazard ratio for death, 1.07 [95 percent confidence interval, 0.62 to 1.86]; P=0.80). The benefit of treatment differed significantly according to the microsatellite-instability status (P=0.01). Adjuvant chemotherapy improved overall survival among patients with microsatellite-stable tumors or tumors exhibiting low-frequency microsatellite instability, according to a multivariate analysis adjusted for stage and grade (hazard ratio for death, 0.72 [95 percent confidence interval, 0.53 to 0.99]; P=0.04). By contrast, there was no benefit of adjuvant chemotherapy in the group with high-frequency microsatellite instability. Fluorouracil-based adjuvant chemotherapy benefited patients with stage II or stage III colon cancer with microsatellite-stable tumors or tumors exhibiting low-frequency microsatellite instability but not those with tumors exhibiting high-frequency microsatellite instability. Copyright 2003 Massachusetts Medical Society

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Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer.

Daniel Sargent, Silvia Marsoni, Geneviève Monges … (2010)

Prior reports have indicated that patients with colon cancer who demonstrate high-level microsatellite instability (MSI-H) or defective DNA mismatch repair (dMMR) have improved survival and receive no benefit from fluorouracil (FU) -based adjuvant therapy compared with patients who have microsatellite-stable or proficient mismatch repair (pMMR) tumors. We examined MMR status as a predictor of adjuvant therapy benefit in patients with stages II and III colon cancer. MSI assay or immunohistochemistry for MMR proteins were performed on 457 patients who were previously randomly assigned to FU-based therapy (either FU + levamisole or FU + leucovorin; n = 229) versus no postsurgical treatment (n = 228). Data were subsequently pooled with data from a previous analysis. The primary end point was disease-free survival (DFS). Overall, 70 (15%) of 457 patients exhibited dMMR. Adjuvant therapy significantly improved DFS (hazard ratio [HR], 0.67; 95% CI, 0.48 to 0.93; P = .02) in patients with pMMR tumors. Patients with dMMR tumors receiving FU had no improvement in DFS (HR, 1.10; 95% CI, 0.42 to 2.91; P = .85) compared with those randomly assigned to surgery alone. In the pooled data set of 1,027 patients (n = 165 with dMMR), these findings were maintained; in patients with stage II disease and with dMMR tumors, treatment was associated with reduced overall survival (HR, 2.95; 95% CI, 1.02 to 8.54; P = .04). Patient stratification by MMR status may provide a more tailored approach to colon cancer adjuvant therapy. These data support MMR status assessment for patients being considered for FU therapy alone and consideration of MMR status in treatment decision making.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Cancer

Journal ID (iso-abbrev): Int. J. Cancer

Journal ID (publisher-id): ijc

Title: International Journal of Cancer. Journal International du Cancer

Publisher: BlackWell Publishing Ltd (Oxford, UK )

ISSN (Print): 0020-7136

ISSN (Electronic): 1097-0215

Publication date (Print): 01 June 2014

Publication date (Electronic): 27 August 2013

Volume: 134

Issue: 11

Pages: 2513-2522

Affiliations

[1 ]Clinical Research Center, St Vincent’s University Hospital, Dublin 4 and UCD School of Medicine and Medical Science, Conway Institute, University College Dublin Dublin, Ireland

[2 ]Medical Department II, Klinikum Grosshadern, Med. Klinik II Munich, Germany

[3 ]Department of Surgery, Helsinki University Central Hospital Helsinki, Finland

[4 ]Department of Oncology, University of Pisa Pisa, Italy

[5 ]Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague Prague, Czech Republic

[6 ]Department of Oncology and Radiotherapy, University Hospital of Pilsen Pilsen, Czech Republic

[7 ]Department of Clinical Biochemistry, Royal Infirmary of Edinburgh Edinburgh, United Kingdom

Author notes

Correspondence to: M.J. Duffy, Clinical Research Center, St Vincent’s University Hospital, Elm Park, Dublin 4, Ireland. Tel.: 353-1-7165814, Fax: 353-1-2696018, E-mail: Michael.J.Duffy@ 123456ucd.ie

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DOI: 10.1002/ijc.28384

PMC ID: 4217376

PubMed ID: 23852704

SO-VID: f3f42c7e-0d39-4e15-845d-3cd5a9960c34

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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update

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Karger: Oncology

Most cited references 122

Systematic review of microsatellite instability and colorectal cancer prognosis.

Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer.

Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer.

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