Value of Mismatch Repair, <i>KRAS</i>, and <i>BRAF</i> Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer

Hutchins, Gordon; Southward, Katie; Handley, Kelly; Magill, Laura; Beaumont, Claire; Stahlschmidt, Jens; Richman, Susan D.; Chambers, P; Seymour, Michel; Kerr, David; Gray, Richard; Quirke, Philip

doi:10.1200/jco.2010.30.1366

Cited by 586 publications

(471 citation statements)

References 43 publications

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“…In addition, Hutchins et al (2011) reported a markedly lower post-surgical recurrence rate in colon cancer patients with dMMR compared to that in patients with pMMR.…”

Section: Discussionmentioning

confidence: 99%

Association between expression of DNA mismatch repair genes and clinical features and prognosis of patients with radical resection of colon cancer

Wang¹,

et al. 2016

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to investigate the clinical significance of the expression of DNA mismatch repair (MMR) genes in patients subjected to radical surgical removal of colon cancer, as well as their correlation with disease prognosis. Ninety stage II and III colon cancer patients who received laparoscopic radical resection of colon cancer at our hospital were recruited in this study. The expression of hMLH1, hMSH2, hMSH6, and hPMS2 in the resected tumor tissues was examined by SP immunohistochemistry, in order to analyze the 2 J.B. Wang et al. Genetics and Molecular Research 15 (3): gmr.15038388 relationship between defective DNA MMR (dMMR) and the clinicopathological features and prognosis of colon cancer. Patients were followed up over a period of 5-35 months, and the Kaplan-Meier survival curve was plotted. dMMR was confirmed in 27 subjects (30.0%), among whom recurrence with metastasis and death was reported in 5 (18.5%) and 2 (7.4%) patients, respectively. The remaining 63 subjects displayed proficient DNA MMR (pMMR); among these, 19 (30.2%) and 7 (11.1%) recurrences with metastasis and death were reported, respectively. dMMR showed no significant correlation with gender, age, or therapeutic modality (P > 0.05), but was significantly correlated with the degree of differentiation, tumor location, number of resected lymph nodes, presence of ileus, and TNM stage (P < 0.05). The prognosis of patients with dMMR was better than that of patients with pMMR. dMMR serves as a biomarker for the prognosis of stage II/III colon cancers.

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“…In addition, Hutchins et al (2011) reported a markedly lower post-surgical recurrence rate in colon cancer patients with dMMR compared to that in patients with pMMR.…”

Section: Discussionmentioning

confidence: 99%

Association between expression of DNA mismatch repair genes and clinical features and prognosis of patients with radical resection of colon cancer

Wang¹,

et al. 2016

Genet. Mol. Res.

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“…Studies also suggest that certain mutations confer a poorer prognosis such as mutations in Ki ras and Braf in stage IV disease [43]. As stated above, the presence of dMMR confers a better prognosis [24], but in our experience does not affect its response to therapy [43]. …”

Section: Molecular Featuresmentioning

confidence: 96%

“…Grade is complicated by the deficient MMR-type cancers which can be classified as high-grade and sometimes mucinous, yet have a good prognosis since they do not metastasise as frequently as MMR-proficient cancers. Immunohistochemistry needs to be used to identify these cancers since they may not require adjuvant therapy as frequently as proficient MMR cancers and have an increased risk of metachronous cancers [23,24,25,26]. …”

Section: Microscopic Featuresmentioning

confidence: 99%

Histopathological Work-Up of Resection Specimens, Local Excisions and Biopsies in Colorectal Cancer

Quirke

Palmer

Hutchins

et al. 2012

Dig Dis

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The pathological examination of material removed from patients with colorectal neoplasia is important. It provides a wide range of information on, for example, the quality and completeness of excision, the stage and biological aggressiveness, the need for further therapy, and response to therapy. Molecular testing adds valuable information on genetic risk and is required before treatment with anti-EGF-r antibodies. This article highlights the value derived from macroscopic inspection of surgical specimens, careful microscopy and excellent reporting according to national guidelines. Increasing use of a number of preoperative therapies and combinations in rectal cancer change the pathological features found and a standardised approach to the diagnosis of complete response is required. It touches upon the issues with frequent changes in TNM staging and the difficulties these changes are causing. The widespread introduction of bowel cancer screening is changing the stage of presentation of colorectal cancer leading to increasing numbers of local excisions and polyp cancers.

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“…Results of this trial showed an approximately 2 to 3% improvement in OS for patients treated with chemotherapy, indicating that chemotherapy provided no benefit for 97% of patients with stage II disease. 74–76 Therefore, the ability to selectively target the highest-risk patients for therapy is clearly needed.…”

Section: Issues In Specific Tumor Typesmentioning

confidence: 99%

NCCN Working Group Report: Designing Clinical Trials in the Era of Multiple Biomarkers and Targeted Therapies

Venook¹,

Arcila²,

Benson³

et al. 2014

J Natl Compr Canc Netw

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Defining treatment susceptible or resistant populations of cancer patients through the use of genetically defined biomarkers has revolutionized cancer care in recent years for some disease/patient groups. Research continues to show that histologically defined diseases are diverse in their expression of unique mutations or other genetic alterations, however, which presents both opportunities for the development of personalized cancer treatments, but increased difficulty in testing these therapies because potential patient populations are divided into ever-smaller numbers. To address some of the growing challenges in biomarker development and clinical trial design, NCCN assembled a group of experts across specialties and solid tumor disease types to begin to define the problems and to consider alternate ways of designing clinical trials in the era of multiple biomarkers and targeted therapies. Results from that discussion are presented, focusing on issues of clinical trial design from the perspective of statisticians, clinical researchers, regulators, pathologists and information developers.

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Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer

Abstract: MMR assays identify patients with a low risk of recurrence. KRAS mutational analysis provides useful additional risk stratification to guide use of chemotherapy.

Cited by 586 publications

References 43 publications

Association between expression of DNA mismatch repair genes and clinical features and prognosis of patients with radical resection of colon cancer

Association between expression of DNA mismatch repair genes and clinical features and prognosis of patients with radical resection of colon cancer

Histopathological Work-Up of Resection Specimens, Local Excisions and Biopsies in Colorectal Cancer

NCCN Working Group Report: Designing Clinical Trials in the Era of Multiple Biomarkers and Targeted Therapies

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