Colorectal Cancer

Colorectal cancer (CRC) is a leading cause of cancer death and the fourth most common form of cancer in the United States. In recent years, both CRC incidence and CRC-related mortality have decreased, which underscores the importance of continued advances in CRC early detection, diagnosis, and care. Although sporadic colon cancers are more common, hereditary colon cancers are also frequent, and identification of these affects screening recommendations both for the individual and family members. CRC screening strategies rely on imaging, laboratory testing, or a combination of the two. Molecular testing of cancer tissue, including evaluation for microsatellite instability (MSI), is recommended to evaluate for Lynch syndrome (LS) risk and to inform prognosis. Monitoring of serum carcinoembryonic antigen (CEA) is recommended following resection of most CRCs to detect recurrence. Laboratory testing may also be used to determine whether particular treatments are likely to be effective.

Tabs Content

Clinical Overview

Quick Answers

Which hereditary syndromes are associated with colorectal cancer, and when is genetic testing for these syndromes recommended?

Approximately one-fifth of colorectal cancers (CRCs) are related to a hereditary syndrome. Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer (HNPCC), accounts for 2-4% of colorectal cancer cases in the United States. Given the frequency of LS, multiple institutions have endorsed immunohistochemistry (IHC) and, in some cases, microsatellite instability (MSI) testing in all colorectal and endometrial cancers to determine which patients should receive germline genetic testing. Other less common syndromes associated with CRC include familial adenomatous polyposis (FAP), MUTYH (MYH)-associated polyposis (MAP), Peutz-Jeghers syndrome (PJS), juvenile polyposis syndrome (JPS), hereditary diffuse gastric cancer, serrated polyposis syndrome, Cowden syndrome, and Li-Fraumeni syndrome. If a familial syndrome is suspected, germline genetic testing, such as a hereditary cancer multigene panel, single gene testing, or familial mutation testing, may be appropriate.

Should vitamin D testing be performed in colorectal cancer?

Multiple studies have suggested that a lack of vitamin D is associated with poorer outcomes in colorectal cancer (CRC); however, other studies have indicated no cancer-specific benefit from vitamin D supplementation. Studies are ongoing, but the National Comprehensive Cancer Network (NCCN) does not currently recommend routine vitamin D testing in patients with CRC.

When should septin9 (SEPT9) methylated DNA testing be used to screen for colorectal cancer?

Septin9 (SEPT9) DNA testing is appropriate in individuals who have refused all other screening tests for colorectal cancer (CRC) and has been FDA approved for this purpose. It is not recommended for routine screening, and the appropriate repeat testing interval has not been determined.

Indications for Testing

Laboratory testing for CRC is used to:

Screen average-risk individuals
Diagnose and inform prognosis in patients with suggestive signs and symptoms or a family history of CRC
Monitor for recurrence
Predict response to treatment

Laboratory Testing

Screening

Screening recommendations for CRC vary. Most guidelines recommend regular CRC screening for individuals 50-75 years of age. Screening may involve visualization (eg, colonoscopy), laboratory testing, or a combination of techniques.

Laboratory Tests for CRC Screening for Persons at Average Risk^a
Test	Recommended Frequency	Description
Stool-Based Tests^b
FIT	Yearly	More accurate than gFOBT Can be performed with single specimen
FOBT (eg, gFOBT)	Yearly	50% of confirmed CRCs have a negative FOBT In at-risk patients, consider sigmoidoscopy or colonoscopy (even in presence of negative FOBT) Positive FOBT requires further evaluation (eg, colonoscopy)
FIT DNA	Not yet determined, but every 3 yrs suggested	Multitargeted stool-based DNA testing; combines FIT with testing for altered DNA biomarkers in cells shed into stool Reasonable alternative to other stool-based and visualization-based tests Greater single-test sensitivity for detecting CRC compared with FIT alone
Serum Test
Test	Recommended Frequency	Description
Septin9 (SEPT9) methylated DNA	Not yet determined	Biomarker for presence of CRC; high negative predictive value For individuals who refuse other screening tests and are ≥50 yrs with average risk and no personal history of polyp removal or CRC and no family history of CRC Not recommended for routine screening
^aAverage risk as defined by ACS: no history of adenoma or IBD; negative family history (having neither first-degree nor second-degree relatives with CRC, nor a clustering of LS-related cancers in the family, and no history of abdominal or pelvic radiation). High-risk patients may require more frequent testing, based on personal or family history of CRC, adenomatous polyp, IBD, or other heritable CRC syndrome; history of abdominal or pelvic radiation. ^bPositive tests require follow-up with direct visualization (eg, colonoscopy) ACS, American Cancer Society; ASCO, American Society of Clinical Oncology; FIT, fecal immunochemical test; FOBT, fecal occult blood test; gFOBT, guaiac fecal occult blood test; IBD, inflammatory bowel disease; NCCN, National Comprehensive Cancer Network Sources: NCCN, 2019; Lopes, 2019

Diagnosis

Initial Workup

The initial laboratory workup for CRC appropriate for resection includes a CBC, chemistry profile, and CEA baseline measurement.

The initial laboratory workup in patients with suspected metastatic synchronous adenocarcinoma includes a CBC, chemistry profile, and CEA measurement. Tumor KRAS/NRAS testing is also recommended, and BRAF testing should be considered (see RAS Somatic Testing and BRAF Somatic Testing, below).

Histopathology

All polyps removed should be examined histologically. Cancer staging is generally performed via the tumor, node, metastases (TNM) system following surgical exploration and pathologic examination.

Molecular Testing

Tissue from a primary, recurrent, or metastatic colorectal tumor is acceptable for somatic molecular testing because results are similar for these specimen types. Formalin-fixed, paraffin-embedded tissue should be used. Germline genetic testing for hereditary CRC syndromes should be based on clinical presentation and family history, and should be performed in conjunction with genetic consultation. A hereditary cancer multigene panel, single gene testing, or familial mutation testing may be appropriate if a hereditary cancer is suspected.

Microsatellite Instability and Mismatch Repair Somatic Testing

Testing for MSI via polymerase chain reaction (PCR), or for mismatch repair (MMR) protein status via immunohistochemistry (IHC), is recommended in all patients with a history of CRC to evaluate for LS risk. MSI (either low or high) or MMR deficiency identifies patients at high risk. See the Lynch Syndrome ARUP Consult topic for more information.

MSI testing is also useful to determine whether to use adjuvant chemotherapy in stage II disease, and both MSI and MMR testing are useful in treatment selection in stage IV disease. High MSI and MMR deficiency are both associated with a more favorable prognosis in stage II disease and decreased likelihood of metastases.

Extended RAS Somatic Testing

Extended RAS gene testing, specifically KRAS (codons 12 and 13 of exon 2; codons 59 and 61 of exon 3; and codons 117 and 146 of exon 4) and NRAS (codons 12 and 13 of exon 2; codons 59 and 61 of exon 3; and codons 117 and 146 of exon 4), is recommended in all patients with CRC at the diagnosis of stage IV disease or being considered for anti-EGFR therapy. Patients with any known KRAS variant in exons 2, 3, or 4 or NRAS variant in exons 2, 3, or 4 should not receive cetuximab or panitumumab. No specific methodology is recommended for RAS testing. Wild-type KRAS is associated with improved prognosis and increased lymph node retrieval.

BRAF Somatic Testing

BRAF testing is recommended in all patients with metastatic CRC at the diagnosis of stage IV disease and should be considered in patients with wild-type KRAS/NRAS metastatic colon cancer. Wild-type BRAF is associated with improved prognosis and increased lymph node retrieval. Presence of the BRAF V600E variant in patients with MMR-deficient CRC tumors with loss of MLH1 suggests sporadic CRC, although it does not rule out Lynch syndrome. Presence of the BRAF V600E variant also decreases the probability that treatment with panitumumab or cetuximab therapy will be effective without anti-BRAF therapy (eg, vemurafenib); combination therapy is recommended. See the NCCN guidelines for specific regimens.

Monitoring

Careful long-term monitoring is recommended following treatment to assess for complications or recurrence. Recommended monitoring includes a combination of imaging (eg, colonoscopy), clinical assessment, and laboratory testing.

Carcinoembryonic Antigen

Laboratory test-based monitoring in CRC includes serum CEA. CEA should be regularly monitored for changes in concentration from a preoperative baseline. A serially elevated postoperative titer suggests recurrence and requires examination. Stage II, III, and IV tumors warrant measurement of CEA every 3-6 months for 2 years after surgery, then every 6 months for a total of 5 years. Routine CEA measurements are not recommended beyond 5 years because most recurrences take place within 5 years of treatment. Follow-up for an elevated CEA should include imaging and clinical assessment until CEA levels stabilize or disease is discovered.

Pharmacogenetics

Fluorouracil Drugs

MSI-low (MSI-L) or microsatellite stable (MSS) tumors are associated with improved outcomes with 5-fluorouracil (5-FU) adjuvant therapy. Patients with low-risk stage II MSI-high (MSI-H) tumors should not be given 5-FU adjuvant therapy. For more information and guidelines on testing for 5-FU sensitivity, see the Germline Pharmacogenetics ARUP Consult topic.

Irinotecan

Decreased UGT1A1 gene expression may lead to drug toxicity, including development of severe neutropenia, from irinotecan. The UGT1A1*28 allele is associated with an increased risk of toxicity. Patients who are heterozygous or homozygous for the *28 allele should receive a reduced starting dose of irinotecan and be treated with caution. Pretreatment testing for UGT1A1*28 should be considered, although guidelines have yet to be established. For additional information and guidelines on UGT1A1 testing, see the Germline Pharmacogenetics ARUP Consult topic.

Fluoropyrimidine

MSI-H status and MMR deficiency are associated with a decreased benefit from fluoropyrimidine adjuvant therapy in stage II disease. Certain variants in the dihydropyrimidine dehydrogenase gene (DYPD) are associated with life-threatening toxicity from fluoropyrimidine. These variants are thought to occur in 1-2% of the population; however, universal testing for these variants before fluoropyrimidine treatment is not currently recommended.

Anti-EGFR Therapy

As mentioned above, patients with any known KRAS variant in exon 2, 3, or 4 or NRAS variant in exon 2, 3, or 4 should not receive cetuximab or panitumumab, and presence of the BRAF V600E variant also decreases the probability that treatment with these drugs will be effective without anti-BRAF therapy. Appropriate treatment regimens are detailed in the NCCN guidelines. HER2 overexpression may also predict resistance to anti-EGFR treatment. However, HER2 testing is not currently recommended for treatment planning.

ARUP Lab Tests

General Screening

Screen for CRC

Occult Blood, Fecal by Immunoassay 2007190

Method: Qualitative Immunoassay

Screen adults of either sex, ≥50 years of age, who have been offered and declined other recommended screening tests

Note: This is a septin9 (SEPT9) methylated DNA test

Epi proColon 2013906

Method: Polymerase Chain Reaction

Screening test for LS

Microsatellite Instability (MSI), HNPCC/Lynch Syndrome, by PCR 0051740

Method: Polymerase Chain Reaction/Fragment Analysis

Preferred screening test for LS in individuals with CRC

Do not use in endometrial cancer

Mismatch Repair by Immunohistochemistry with Reflex to BRAF Codon 600 Mutation and MLH1 Promoter Methylation 2002327

Method: Qualitative Immunohistochemistry/Qualitative Real-time Polymerase Chain Reaction

For additional information on tests for LS, see the Lynch Syndrome ARUP Consult topic and testing algorithm.

Recommended test to confirm a diagnosis of hereditary gastrointestinal (GI) cancer in individuals with a personal or family history of GI cancer and/or polyposis when a familial variant is unknown

Includes all four MMR genes known to cause LS

Hereditary Gastrointestinal Cancer Panel, Sequencing and Deletion/Duplication 2013449

Method: Massively Parallel Sequencing/Exonic Oligonucleotide-based CGH Microarray/Sequencing/Multiplex Ligation-dependent Probe Amplification

Recommended test to confirm diagnosis of hereditary cancer syndrome in individuals with personal or family history consistent with features of more than one cancer syndrome

Hereditary Cancer Panel, Sequencing and Deletion/Duplication 2012032

Method: Massively Parallel Sequencing/Exonic Oligonucleotide-based CGH Microarray

Useful when a pathogenic familial variant identifiable by sequencing is known

Familial Mutation, Targeted Sequencing 2001961

Method: Polymerase Chain Reaction/Sequencing

For more information about diagnostic testing for LS, including specific MMR gene testing, see the Lynch Syndrome ARUP consult topic and testing algorithm.

Assess for targeted variants that are useful for prognosis and/or treatment of individuals with solid tumor cancers

For additional test information, refer to the Solid Tumor Mutation Panel Test Fact Sheet

Solid Tumor Mutation Panel by Next Generation Sequencing 2007991

Method: Massively Parallel Sequencing

Monitor patient for tumor recurrence

Carcinoembryonic Antigen 0080080

Method: Quantitative Electrochemiluminescent Immunoassay

Determine eligibility for anti-EGFR (cetuximab and panitumumab) therapy in patients with metastatic CRC

Does not include all codons recommended as part of extended RAS testing

KRAS Mutation Detection with Reflex to BRAF Codon 600 Mutation Detection 2001932

Method: Polymerase Chain Reaction/ Pyrosequencing

Predict response to anti-EGFR and MAPK pathway therapies in a variety of malignancies, including CRC

Does not include all codons recommended as part of extended RAS testing

KRAS Mutation Detection 0040248

Method: Polymerase Chain Reaction/Pyrosequencing

Detect activating BRAF mutations at codon 600, which can indicate resistance to anti-EGFR therapy in CRC

Also used within LS reflex testing pathway (for CRC specimens only)

BRAF Codon 600 Mutation Detection by Pyrosequencing 2002498

Method: Polymerase Chain Reaction/Pyrosequencing

Determine BRAF V600E mutation status in patients with solid tumors to select candidates for targeted therapy with kinase (BRAF and/or MEK) inhibitors; monitor response to therapy and disease progression in patients carrying BRAF V600E mutation

BRAF V600E Mutation Detection in Circulating Cell-Free DNA by Digital Droplet PCR 2013921

Method: Polymerase Chain Reaction

Predict response to anti-EGFR and MAPK pathway therapies in a variety of malignancies, including CRCs; detect activating NRAS mutations associated with relative resistance to anti-EGFR therapy

Does not include all codons recommended as part of extended RAS testing

NRAS Mutation Detection by Pyrosequencing 2003123

Method: Polymerase Chain Reaction/Pyrosequencing

Predict risk of dose-related toxicity to 5-FU therapy

Dihydropyrimidine Dehydrogenase (DPYD), 3 Variants 2012166

Method: Polymerase Chain Reaction/Fluorescence Monitoring

Use for dosage planning for individuals who will receive high-dose irinotecan (>150 mg/m²), have personal or family history of sensitivity to irinotecan, or have experienced neutropenia while receiving irinotecan

UDP Glucuronosyltransferase 1A1 (UGT1A1) Genotyping 0051332

Method: Polymerase Chain Reaction/Fragment Analysis

Test Fact Sheet(s)

Hereditary Cancer Panel

Lynch Syndrome/Hereditary Nonpolyposis Colorectal Cancer

Hereditary Gastrointestinal Cancer Panel, Including Lynch Syndrome

Familial Adenomatous Polyposis and MUTYH-Associated Polyposis

UGT1A1 Gene Analysis

Dihydropyrimidine Dehydrogenase (DPYD), 3 Variants

Medical Experts

Bayrak-Toydemir, Pinar, MD, PhD, FACMG, Medical Director, Molecular Genetics and Genomics, at ARUP Laboratories; Professor of Clinical Pathology, University of Utah

Matynia, Anna P., MD, Medical Director, Solid Tumor Molecular Diagnostics, at ARUP Laboratories; Assistant Professor of Clinical Pathology, University of Utah

Wiley, Samantha, MS, LCGC, Genetic Counselor, Molecular Genetics, at ARUP Laboratories

References

NCCN Clinical Practice Guidelines in Oncology, Colon Cancer. Version 4.2019. National Comprehensive Cancer Network. Fort Washington, PA [Updated: Nov 2019; Accessed: Nov 2019]
Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL, Guideline Development Group, American College of Medical Genetics and Genomics Professional Practice and Guidelines Committee and National Society of Genetic Counselors Practice Guidelines Committee. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med. 2015; 17(1): 70-87. PubMed
NCCN Clinical Practice Guidelines in Oncology, Genetic/Familial High-Risk Assessment: Colorectal. Version 2.2019. National Comprehensive Cancer Network. Fort Washington, PA [Updated: Aug 2019; Accessed: Dec 2019]
NCCN Clinical Practice Guidelines in Oncology, Colorectal Cancer Screening. Version 2.2019. National Comprehensive Cancer Network. Fort Washington, PA [Updated: Aug 2019; Accessed: Dec 2019]
Lopes G, Stern MC, Temin S, Sharara AI, Cervantes A, Costas-Chavarri A, Engineer R, Hamashima C, Ho GF, Huitzil FD, Moghani MM, Nandakumar G, Shah MA, Teh C, Manjarrez SE, Verjee A, Yantiss R, Correa MC. Early Detection for Colorectal Cancer: ASCO Resource-Stratified Guideline. J Glob Oncol. 2019; 5: 1-22. PubMed
American Cancer Society Guideline for Colorectal Cancer Screening. For people at average risk. American Cancer Society. [Revised: May 2018; Accessed: Dec 2019]
Lin JS, Piper MA, Perdue LA, Rutter CM, Webber EM, O'Connor E, Smith N, Whitlock EP. Screening for Colorectal Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2016; 315(23): 2576-94. PubMed

Additional Resources

American Cancer Society Colorectal Cancer Screening Tests. American Cancer Society. [Accessed: Dec 2019]

American Cancer Society Guidelines for the Early Detection of Cancer. American Cancer Society. Atlanta, GA [Revised: May 2018; Accessed: Dec 2019]

American Cancer Society Tests to Diagnose and Stage Colorectal Cancer. American Cancer Society. [Revised: Aug 2018; Accessed: Dec 2019]

Balmana J, Balaguer F, Cervantes A, Arnold D, ESMO Guidelines Working Group. Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines. Ann Oncol. 2013; 24 Suppl 6: vi73-80. PubMed

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Bénard F, Barkun AN, Martel M, von Renteln D. Systematic review of colorectal cancer screening guidelines for average-risk adults: Summarizing the current global recommendations. World J Gastroenterol. 2018; 24(1): 124-138. PubMed

Caudle KE, Thorn CF, Klein TE, Swen JJ, McLeod HL, Diasio RB, Schwab M. Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing. Clin Pharmacol Ther. 2013; 94(6): 640-5. PubMed

Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Aug 2019]

Chua W, Moore MM, Charles KA, Clarke SJ. Predictive biomarkers of clinical response to targeted antibodies in colorectal cancer. Curr Opin Mol Ther. 2009; 11(6): 611-22. PubMed

Colle R, Cohen R, Cochereau D, Duval A, Lascols O, Lopez-Trabada D, Afchain P, Trouilloud I, Parc Y, Lefevre JH, Fléjou J, Svrcek M, André T. Immunotherapy and patients treated for cancer with microsatellite instability. Bull Cancer. 2017; 104(1): 42-51. PubMed

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Fearon ER. Molecular genetics of colorectal cancer. Annu Rev Pathol. 2011; 6: 479-507. PubMed

Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL, Guideline Development Group, American College of Medical Genetics and Genomics Professional Practice and Guidelines Committee and National Society of Genetic Counselors Practice Guidelines Committee. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med. 2015; 17(1): 70-87. PubMed

Hegde M, Ferber M, Mao R, Samowitz W, Ganguly A, Working Group of the American College of Medical Genetics and Genomics (ACMG) Laboratory Quality Assurance Committee. ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (Lynch syndrome, familial adenomatous polyposis, and MYH-associated polyposis). Genet Med. 2014; 16(1): 101-16. PubMed

Helsingen LM, Vandvik PO, Jodal HC, Agoritsas T, Lytvyn L, Anderson JC, Auer R, Murphy SB, Almadi MA, Corley DA, Quinlan C, Fuchs JM, McKinnon A, Qaseem A, Heen AF, Siemieniuk RA, Kalager M, Usher-Smith JA, Lansdorp-Vogelaar I, Bretthauer M, Guyatt G. Colorectal cancer screening with faecal immunochemical testing, sigmoidoscopy or colonoscopy: a clinical practice guideline. BMJ. 2019; 367: l5515. PubMed

Impact of primary (1º) tumor location on overall survival (OS) and progression-free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB/SWOG 80405 (Alliance). J Clin Oncol. 34, 2016 (suppl; abstr 3504) [Accessed: Dec 2019]

Liu Z, Zhang Y, Niu Y, Li K, Liu X, Chen H, Gao C. A systematic review and meta-analysis of diagnostic and prognostic serum biomarkers of colorectal cancer. PLoS One. 2014; 9(8): e103910. PubMed

Newton KF, Newman W, Hill J. Review of biomarkers in colorectal cancer. Colorectal Dis. 2012; 14(1): 3-17. PubMed

Protocol for the Examination of Specimens from Patients with Primary Carcinoma of the Colon and Rectum. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: Oct 2013. College of American Pathologists (CAP). Northfield, IL [Revised: Jan 2016; Accessed: Dec 2019]

Qaseem A, Crandall CJ, Mustafa RA, Hicks LA, Wilt TJ, Clinical Guidelines Committee of the American College of Physicians. Screening for Colorectal Cancer in Asymptomatic Average-Risk Adults: A Guidance Statement From the American College of Physicians. Ann Intern Med. 2019; 171(9): 643-654. PubMed

Rex DK, Boland R, Dominitz JA, Giardiello FM, Johnson DA, Kaltenbach T, Levin TR, Lieberman D, Robertson DJ. Colorectal Cancer Screening: Recommendations for Physicians and Patients from the U.S. Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. 2017; 112(7): 1016-1030. PubMed

Rex DK, Johnson DA, Anderson JC, Schoenfeld PS, Burke CA, Inadomi JM, American College of Gastroenterology. American College of Gastroenterology guidelines for colorectal cancer screening 2009 [corrected]. Am J Gastroenterol. 2009; 104(3): 739-50. PubMed

Ross JS. Clinical implementation of KRAS testing in metastatic colorectal carcinoma: the pathologist's perspective. Arch Pathol Lab Med. 2012; 136(10): 1298-307. PubMed

Sepulveda AR, Hamilton SR, Allegra CJ, Grody W, Cushman-Vokoun AM, Funkhouser WK, Kopetz SE, Lieu C, Lindor NM, Minsky BD, Monzon FA, Sargent DJ, Singh VM, Willis J, Clark J, Colasacco C, Rumble B, Temple-Smolkin R, Ventura CB, Nowak JA. Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and the American Society of Clinical Oncology. J Clin Oncol. 2017; JCO2016719807. PubMed

Sharma SG, Gulley ML. BRAF mutation testing in colorectal cancer. Arch Pathol Lab Med. 2010; 134(8): 1225-8. PubMed

Song L, Li Y. SEPT9: A Specific Circulating Biomarker for Colorectal Cancer. Adv Clin Chem. 2015; 72: 171-204. PubMed

Stoffel EM, Mangu PB, Gruber SB, Hamilton SR, Kalady MF, Lau MW, Lu KH, Roach N, Limburg PJ, American Society of Clinical Oncology, European Society of Clinical Oncology. Hereditary colorectal cancer syndromes: American Society of Clinical Oncology Clinical Practice Guideline endorsement of the familial risk-colorectal cancer: European Society for Medical Oncology Clinical Practice Guidelines. J Clin Oncol. 2015; 33(2): 209-17. PubMed

Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, Aguilar A, Bardelli A, Benson A, Bodoky G, Ciardiello F, D'Hoore A, Diaz-Rubio E, Douillard J, Ducreux M, Falcone A, Grothey A, Gruenberger T, Haustermans K, Heinemann V, Hoff P, Köhne C, Labianca R, Laurent-Puig P, Ma B, Maughan T, Muro K, Normanno N, Österlund P, Oyen WJ, Papamichael D, Pentheroudakis G, Pfeiffer P, Price TJ, Punt C, Ricke J, Roth A, Salazar R, Scheithauer W, Schmoll HJ, Tabernero J, Taïeb J, Tejpar S, Wasan H, Yoshino T, Zaanan A, Arnold D. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016; 27(8): 1386-422. PubMed

Venook AP. Metastatic Colorectal Cancer: Lessons Learned, Future Possibilities. J Natl Compr Canc Netw. 2016; 14(5 Suppl): 666-8. PubMed

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Resources from the ARUP Institute for Clinical and Experimental Pathology®

Affolter K, Gligorich K, Samadder NJ, Samowitz WS, Curtin K. Feasibility of Large-Scale Identification of Sessile Serrated Polyp Patients Using Electronic Records: A Utah Study. Dig Dis Sci. 2017; 62(6): 1455-1463. PubMed

Affolter K, Samowitz W, Tripp S, Bronner MP. BRAF V600E mutation detection by immunohistochemistry in colorectal carcinoma. Genes Chromosomes Cancer. 2013; 52(8): 748-52. PubMed

Patil DT, Bronner MP, Portier BP, Fraser CR, Plesec TP, Liu X. A five-marker panel in a multiplex PCR accurately detects microsatellite instability-high colorectal tumors without control DNA. Diagn Mol Pathol. 2012; 21(3): 127-33. PubMed

Pellatt DF, Stevens JR, Wolff RK, Mullany LE, Herrick JS, Samowitz W, Slattery ML. Expression Profiles of miRNA Subsets Distinguish Human Colorectal Carcinoma and Normal Colonic Mucosa. Clin Transl Gastroenterol. 2016; 7: e152. PubMed

Salk JJ, Bansal A, Lai LA, Crispin DA, Ussakli CH, Horwitz MS, Bronner MP, Brentnall TA, Loeb LA, Rabinovitch PS, Risques RA. Clonal expansions and short telomeres are associated with neoplasia in early-onset, but not late-onset, ulcerative colitis. Inflamm Bowel Dis. 2013; 19(12): 2593-602. PubMed

Samadder J, Burt RW, Toydemir RM. Developmental Delay and Colon Polyposis. Gastroenterology. 2017; 153(4): 908-909. PubMed

Samadder J, Neklason DW, Boucher KM, Byrne KR, Kanth P, Samowitz W, Jones D, Tavtigian SV, Done MW, Berry T, Jasperson K, Pappas L, Smith L, Sample D, Davis R, Topham MK, Lynch P, Strait E, McKinnon W, Burt RW, Kuwada SK. Effect of Sulindac and Erlotinib vs Placebo on Duodenal Neoplasia in Familial Adenomatous Polyposis: A Randomized Clinical Trial. JAMA. 2016; 315(12): 1266-75. PubMed

Samadder J, Valentine JF, Guthery S, Singh H, Bernstein CN, Wan Y, Wong J, Boucher K, Pappas L, Rowe K, Bronner M, Ulrich CM, Burt RW, Curtin K, Smith KR. Colorectal Cancer in Inflammatory Bowel Diseases: A Population-Based Study in Utah. Dig Dis Sci. 2017; 62(8): 2126-2132. PubMed

Shaco-Levy R, Jasperson KW, Martin K, Samadder J, Burt RW, Ying J, Bronner MP. Morphologic characterization of hamartomatous gastrointestinal polyps in Cowden syndrome, Peutz-Jeghers syndrome, and juvenile polyposis syndrome. Hum Pathol. 2016; 49: 39-48. PubMed

Shaco-Levy R, Jasperson KW, Martin K, Samadder NJ, Burt RW, Ying J, Bronner MP. Gastrointestinal Polyposis in Cowden Syndrome. J Clin Gastroenterol. 2017; 51(7): e60-e67. PubMed

Slattery ML, Herrick JS, Mullany LE, Valeri N, Stevens J, Caan BJ, Samowitz W, Wolff RK. An evaluation and replication of miRNAs with disease stage and colorectal cancer-specific mortality. Int J Cancer. 2015; 137(2): 428-38. PubMed

Slattery ML, Herrick JS, Pellatt DF, Stevens JR, Mullany LE, Wolff E, Hoffman MD, Samowitz WS, Wolff RK. MicroRNA profiles in colorectal carcinomas, adenomas and normal colonic mucosa: variations in miRNA expression and disease progression. Carcinogenesis. 2016; 37(3): 245-61. PubMed

Szankasi P, Reading S, Vaughn CP, Prchal JT, Bahler DW, Kelley TW. A quantitative allele-specific PCR test for the BRAF V600E mutation using a single heterozygous control plasmid for quantitation: a model for qPCR testing without standard curves. J Mol Diagn. 2013; 15(2): 248-54. PubMed

Tomsic J, Senter L, Liyanarachchi S, Clendenning M, Vaughn CP, Jenkins MA, Hopper JL, Young J, Samowitz W, de la Chapelle A. Recurrent and founder mutations in the PMS2 gene. Clin Genet. 2013; 83(3): 238-43. PubMed

Vaughn CP, Baker CL, Samowitz WS, Swensen JJ. The frequency of previously undetectable deletions involving 3' Exons of the PMS2 gene. Genes Chromosomes Cancer. 2013; 52(1): 107-12. PubMed

Walter AW, Ennis S, Best H, Vaughn CP, Swensen JJ, Openshaw A, Gripp KW. Constitutional mismatch repair deficiency presenting in childhood as three simultaneous malignancies. Pediatr Blood Cancer. 2013; 60(11): E135-6. PubMed

Educational Videos

Content Review:

December 2019

Last Update: January 2020

Colorectal Cancer

Quick Answers

Which hereditary syndromes are associated with colorectal cancer, and when is genetic testing for these syndromes recommended?

Should vitamin D testing be performed in colorectal cancer?

When should septin9 (SEPT9) methylated DNA testing be used to screen for colorectal cancer?

Indications for Testing

Laboratory Testing

Screening

Diagnosis

Initial Workup

Histopathology

Molecular Testing

Microsatellite Instability and Mismatch Repair Somatic Testing

Extended RAS Somatic Testing

BRAF Somatic Testing

Monitoring

Carcinoembryonic Antigen

Pharmacogenetics

Fluorouracil Drugs

Irinotecan

Fluoropyrimidine

Anti-EGFR Therapy

ARUP Lab Tests

Screening for Colorectal Cancer

Screening for Lynch Syndrome

Diagnosis of Lynch or Other Hereditary Cancer Syndromes

Solid Tumor Prognostic and Treatment Testing

Monitoring

Pharmacogenetics

Test Fact Sheet(s)

Medical Experts

References

Additional Resources

Resources from the ARUP Institute for Clinical and Experimental Pathology®

ARUP Laboratories

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	Colorectal Cancer. ARUP Consult^©. Retrieved January 14, 2020, from: https://arupconsult.com/content/colorectal-cancer

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Colorectal Cancer

Quick Answers

Which hereditary syndromes are associated with colorectal cancer, and when is genetic testing for these syndromes recommended?

Should vitamin D testing be performed in colorectal cancer?

When should septin9 (SEPT9) methylated DNA testing be used to screen for colorectal cancer?

Indications for Testing

Laboratory Testing

Screening

Diagnosis

Initial Workup

Histopathology

Molecular Testing

Microsatellite Instability and Mismatch Repair Somatic Testing

Extended RAS Somatic Testing

BRAF Somatic Testing

Monitoring

Carcinoembryonic Antigen

Pharmacogenetics​

Fluorouracil Drugs

Irinotecan​

Fluoropyrimidine​

Anti-EGFR Therapy

ARUP Lab Tests

Screening for Colorectal Cancer

Screening for Lynch Syndrome

Diagnosis of Lynch or Other Hereditary Cancer Syndromes

Solid Tumor Prognostic and Treatment Testing

Monitoring

Pharmacogenetics

Test Fact Sheet(s)

Medical Experts

References

Additional Resources

Resources from the ARUP Institute for Clinical and Experimental Pathology®

ARUP Laboratories

ARUP Websites

ARUP Consult

Pharmacogenetics

Irinotecan

Fluoropyrimidine