scholarly journals Mismatch repair polymorphisms and risk of colon cancer, tumour microsatellite instability and interactions with lifestyle factors

Gut ◽  
2008 ◽  
Vol 58 (5) ◽  
pp. 661-667 ◽  
Author(s):  
P T Campbell ◽  
K Curtin ◽  
C M Ulrich ◽  
W S Samowitz ◽  
J Bigler ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Lifestyle Factors

Sporadic Colon Cancer: Mismatch Repair Immunohistochemistry and Microsatellite Instability in Omani Subjects

2008 ◽  
Vol 53 (10) ◽  
pp. 2723-2731 ◽  
Author(s):  
Hassan Ashktorab ◽  
Hassan Brim ◽  
Marwa Al-Riyami ◽  
Anand Date ◽  
Kamla Al-Mawaly ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Sporadic Colon Cancer

Profiling for microsatellite instability (MSI) and mismatch repair (MMR) among patients with colon cancer in real world settings.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e15622-e15622
Author(s):  
Tracy Ann Proverbs-Singh ◽  
John Marshall ◽  
Marian M Varda ◽  
Ibrahim Nakhoul ◽  
Bhavesh Balar ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Real World

scholarly journals Microsatellite Instability Predicts Improved Response to Adjuvant Therapy With Irinotecan, Fluorouracil, and Leucovorin in Stage III Colon Cancer: Cancer and Leukemia Group B Protocol 89803

2009 ◽  
Vol 27 (11) ◽  
pp. 1814-1821 ◽  
Author(s):  
Monica M. Bertagnolli ◽  
Donna Niedzwiecki ◽  
Carolyn C. Compton ◽  
Hejin P. Hahn ◽  
Margaret Hall ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Stage Iii ◽  
Stage Iii Colon Cancer ◽  
End Point ◽  
Colon Cancers ◽  
Weekly Bolus ◽  
Group B ◽  
Leukemia Group

Purpose Colon cancers exhibiting DNA mismatch repair (MMR) defects demonstrate distinct clinical and pathologic features, including better prognosis and reduced response to fluorouracil (FU) –based chemotherapy. This prospective study investigated adjuvant chemotherapy containing FU and irinotecan in patients with MMR deficient (MMR-D) colon cancers. Patients and Methods Cancer and Leukemia Group B 89803 randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly bolus FU/leucovorin (LV) or weekly bolus irinotecan, FU, and LV (IFL). The primary end point was overall survival; disease-free survival (DFS) was a secondary end point. Tumor expression of the MMR proteins, MLH1 and MSH2, was determined by immunohistochemistry (IHC). DNA microsatellite instability was also assessed using a panel of mono- and dinucleotide markers. Tumors with MMR defects were those demonstrating loss of MMR protein expression (MMR-D) and/or microsatellite instability high (MSI-H) genotype. Results Of 723 tumor cases examined by genotyping and IHC, 96 (13.3%) were MMR-D/MSI-H. Genotyping results were consistent with IHC in 702 cases (97.1%). IFL-treated patients with MMR-D/MSI-H tumors showed improved 5-year DFS as compared with those with mismatch repair intact tumors (0.76; 95% CI, 0.64 to 0.88 v 0.59; 95% CI, 0.53 to 0.64; P = .03). This relationship was not observed among patients treated with FU/LV. A trend toward longer DFS was observed in IFL-treated patients with MMR-D/MSI-H tumors as compared with those receiving FU/LV (0.57; 95% CI, 0.42 to 0.71 v 0.76; 95% CI, 0.64 to 0.88; P = .07; hazard ratio interaction between tumor status and treatment, 0.51; likelihood ratio P = .117). Conclusion Loss of tumor MMR function may predict improved outcome in patients treated with the IFL regimen as compared with those receiving FU/LV.

scholarly journals Genomic Profiling for KRAS, NRAS, BRAF, Microsatellite Instability, and Mismatch Repair Deficiency Among Patients With Metastatic Colon Cancer

2019 ◽  
pp. 1-9 ◽  
Author(s):  
Martin E. Gutierrez ◽  
Kristin S. Price ◽  
Richard B. Lanman ◽  
Rebecca J. Nagy ◽  
Irfan Shah ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
De Novo ◽  
The United States ◽  
Metastatic Colon Cancer ◽  
Mismatch Repair Deficiency ◽  
National Guidelines ◽  
Repair Deficiency ◽  
Biomarker Testing

PURPOSE Genomic testing is recognized in national guidelines as essential to guide appropriate therapy selection in metastatic colorectal cancer. Previous studies report adherence to testing guidelines is suboptimal, but current testing rates have not been assessed. This study reports testing rates in metastatic colon cancer (mCC) for guideline-recommended biomarkers in a US-based population. MATERIALS AND METHODS A retrospective review of data extracted from electronic medical records was performed to identify patients with pathologically confirmed mCC and describe patterns of guideline-aligned biomarker testing. Data were extracted from the electronic health records of 1,497 patients treated at 23 practices across the United States. Both community and academic centers were represented. RESULTS A total of 1,497 patients with mCC diagnosed between January 1, 2013 and December 31, 2017 were identified. Guideline-aligned biomarker testing rates for RAS, BRAF, and microsatellite instability/mismatch repair deficiency over this study period were 41%, 43%, and 51%, respectively. Patients were more likely to have guideline-aligned testing for RAS and BRAF if they were treated at an academic center, were diagnosed with de novo metastatic disease, and were female. In addition, patients < 65 years of age were more likely to have guideline-aligned RAS testing. Of the 177 patients (12% of cohort) who received anti–epidermal growth factor receptor therapy, only 50 (28%) had complete guideline-aligned biomarker testing. CONCLUSION Despite guideline recommendations and significant therapeutic implications, overall biomarker testing rates in mCC remain suboptimal. Adherence to guideline-recommended biomarker testing would potentially reduce exposure to expensive and ineffective therapies, resulting in improved patient outcomes.

Retrospective review of colorectal cancer specimens in individuals younger than age 50 for microsatellite instability testing and DNA mismatch repair enzyme expression.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 392-392
Author(s):  
N. Durie ◽  
H. Staszewski ◽  
T. Palaia ◽  
L. Ragolia ◽  
W. Nugent
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Microsatellite Instability ◽  
Cancer Patients ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Mononucleotide Repeat ◽  
Repair Enzyme ◽  
Dna Mismatch ◽  
Colorectal Cancer Patients

392 Background: Data from studies performed at tertiary referral centers suggest that the yield of patients with the underlying defect in hereditary non-polyposis colon cancer (HNPCC) could be improved by screening every colon cancer for the phenotypic expression of the MMR defect by immunohistochemistry (IHC) and/or an assay for microsatellite instability (MSI). We propose to determine the incidence of microsatellite unstable colon cancers and the incidence of absence of expression of DNA MMR enzymes in de-identified colorectal cancer specimens from patients under the age of 50 who have presented to Winthrop University Hospital over the past ten years. This incidence will be compared with those suggested by recent large retrospective studies in tertiary care centers. Methods: Immunoperoxidase staining for MLH1, MSH2, MSH6 and PMS2 were performed on formalin-fixed tissue. MSI assays were performed on microdissected DNA from paraffin-embedded tissue blocks. All cases were tested with five mononucleotide repeat markers (BAT-25, BAT-26, NR-21, NR-24 and MONO-27) and two pentanucleotide repeat markers (Penta C and Penta D). Tumor samples in which two or more altered monoclonal repeat markers were found out of five were classified as MSI-H. Results: Screening for expression of DNA mismatch repair enzymes and MSI in an enriched selected (by age <50) population of colorectal cancer patients resulted in detection of 7/51 (14%) specimens that were MSI-H and 7/61 (12%) that were “positive” for lack of expression of at least one DNA mismatch repair enzyme. Conclusions: Our results are similar to those reported in the literature in unselected series of patients with colorectal cancer. IHC staining or MSI analysis alone may be insufficient in selecting those colorectal cancer patients that should be referred for genetic testing for HNPCC. However, screening of an unselected population with both these modalities should have a low but clinically significant yield. Since other research have shown that traditional criteria such as the Bethesda guidelines are inadequate, we support the use of both measures prospectively in all colorectal cancer patients. No significant financial relationships to disclose.

Rates of genotyping for KRAS, NRAS, BRAF, microsatellite instability (MSI), and mismatch repair (MMR) in metastatic colon cancer patients: Gaps and implications.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15123-e15123
Author(s):  
Martin Gutierrez ◽  
Kristin Sedgwick Price ◽  
Richard B. Lanman ◽  
Rebecca Nagy ◽  
Irfan Shah ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Real World ◽  
The United States ◽  
Treatment Selection ◽  
Optimal Treatment ◽  
Braf V600e ◽  
Metastatic Colon Cancer ◽  
Molecular Genotyping

e15123 Background: Molecular genotyping is essential to optimal treatment selection in metastatic colon cancer (mCC) as mutations in exons 2,3,4 of KRAS and NRAS (expanded RAS) and BRAF V600E predict lack of response to anti-HER2 therapy, and microsatellite instability high (MSI-H) predicts positive response to immune checkpoint inhibitor (ICPI)s. The National Comprehensive Cancer Network (NCCN) first recommended molecular genotyping for mCC in 2009 and by 2016 recommended all pts with mCC have expanded RAS, BRAF, and mismatch repair deficiency (MMRd) testing. This study updates genotyping rates in metastatic colon cancer (mCC) in a real-world practice setting. Methods: We performed a retrospective review of genomic testing patterns from pts with mCC diagnosed between January 2013 and December 2017 from 22 academic and community health centers in the United States who contributed to COTA’s de-identified Real World Evidence database. Results: 563 pts with mCC were identified in the Cota database over the 5-year period. 341 (61%) pts with mCC had testing for KRAS, 130 (23%) for NRAS, 177 (31%) for BRAF, and 297 (53%) for MMRd. Testing rates for NRAS, BRAF and MMRd all increased from 2013 to 2017 but remained suboptimal with undergenotyping rates of 48%, 45% and 12% respectively by 2017. 33 (6%) pts received cetuximab and/or panitumumab without prior testing for both KRAS and NRAS, despite established lack of benefit. Between 2016 and 2017, when NCCN recommended testing for KRAS, NRAS, BRAF and MMRd, only 24% of mCC pts were tested for all biomarkers. Conclusions: Although molecular genotyping rates increased over the described 5-year period, since 2016, less than one quarter of all mCC pts in this cohort received guideline recommended genotyping. Approaches that may improve complete genotyping rates in mCC, such as plasma-based comprehensive genomic profiling, may improve optimal treatment selection and should be tested in prospective trials.

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