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Lynch Syndrome: Laboratory Support of Diagnosis and Management

Lynch Syndrome: Laboratory Support of Diagnosis and Management

Clinical Focus

Lynch Syndrome

Laboratory Support of Diagnosis and Management



Clinical Background

Table 1:  Lifetime Cancer Risk in Individuals with Lynch Syndrome

Individuals Suitable for Testing

Table 2: Bethesda Guidelines for Testing Colorectal Tumors for Microsatellite Instability (MSI)

Table 3 : Amsterdam II Criteria for Identifying Families with Lynch Syndrome

Test Availability

Table 4: Tests Available for Diagnosis and Management of Lynch Syndrome

Test Selection and Interpretation

Figure 1: Suggested Laboratory Testing for the Diagnosis of Lynch Syndrome

Figure 2: Lynch Syndrome Diagnosis: Suggested Follow-up Testing for Patients with Abnormal IHC Results

Figure 3: Lynch Syndrome Diagnosis: Unaffected Family Members at Risk for Lynch Syndrome


Clinical Background [return to contents]

Colorectal Cancer Overview

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States, with projections of 49,000 deaths and 134,000 new cases diagnosed in 2016.1 About three-quarters of CRC cases are sporadic.2 The remaining are familial (20%) or inherited (5% to 10%).2,3 Familial CRC is not well understood and is characterized by an increased risk of CRC and an unclear pattern of inheritance. Inherited CRC, on the other hand, is caused by a germline mutation and exhibits a clear pattern of inheritance. Inherited CRC includes Lynch syndrome (formerly known as hereditary nonpolyposis colorectal cancer [HNPCC]) as well as other less common syndromes. Whether colorectal cancer is sporadic, familial, or inherited has important implications for screening and follow-up of patients and their family members.

Lynch Syndrome

Lynch syndrome is caused by a pathogenic germline variant in a mismatch repair (MMR) gene (MLH1, MSH2, MSH6, and PMS2) or in the EPCAM gene. These variants result in a defective MMR process in which nucleotide mismatches that occur during DNA replication are not repaired. Another consequence is insertions or deletions of nucleotides within repeated DNA nucleotide sequences known as microsatellites, ie, microsatellite instability (MSI). In Lynch syndrome, 1 copy of a defective MMR allele is inherited. Subsequent somatic alteration of the normal allele leads to the progression of a benign adenoma to CRC.4

Lynch syndrome is characterized by a higher lifetime cancer risk and, typically, an earlier age of onset than in the general population (Table 1).5 Patients with Lynch syndrome have an increased risk of cancer in the colon, rectum, stomach, small intestine, hepatobiliary tract, urinary tract, brain, skin, and pancreas.5,6 Women with the syndrome also have an increased risk for endometrial and ovarian cancers.

Table 1. Lifetime Cancer Risk in Individuals with Lynch Syndrome5-15

Cancer Type

Cancer Risk in
General Population (%)

People with Lynch Syndromea

Cancer Risk (%)

Mean Age at Diagnosis (years)

















Small intestine




Sebaceous neoplasm



Not reported




Not reported

Hepatobiliary tract



Not reported

Urinary tract








CNS, central nervous system.


Data are from MLH1 and MSH2 mutation carriers ≤70 years of age. Risks for MSH6 and PMS2 mutation carriers are lower (see reference 6).

Among patients with Lynch syndrome, early detection and removal of colorectal adenomas and carcinomas is critical. Surveillance colonoscopy enables their detection and removal at an earlier stage and is associated with decreased CRC-specific mortality.16,17 Furthermore, a Lynch syndrome diagnosis in the family may foster testing of blood relatives and early initiation of surveillance if an MMR gene mutation is found.

Individuals Suitable for Testing [return to contents]

  • Individuals with CRC at any age or endometrial cancer at <50 years of age

  • Individuals who have 2 or more Lynch syndrome-related cancers

  • Individuals who have a blood relative with Lynch syndrome

  • Individuals with a strong family history of Lynch syndrome cancers

The National Comprehensive Cancer Network® (NCCN) recommends that testing for Lynch syndrome be considered for all previously untested individuals with CRC.6 This approach has been incorporated into guidelines approved by the American College of Gastroenterology, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the American Society of Colon and Rectal Surgeons.18 The approach identifies more patients with Lynch syndrome than selecting patients based on the personal and family history factors outlined in the Bethesda guidelines (Table 2).19

NCCN also provides an alternative recommendation for testing those with a CRC diagnosis: test all individuals diagnosed with CRC at <70 years of age and those ≥70 years of age if they meet the Bethesda guidelines. 

NCCN further recommends testing individuals if they meet Bethesda guidelines or Amsterdam criteria (Table 3), have been diagnosed with endometrial cancer before age 50, have a blood relative with Lynch syndrome, or have a ≥5% risk for Lynch syndrome based on computer models (MMRPro, PREMM[1,2,6], or MMRpredict). These models use personal and family history to  calculate the likelihood of an individual carrying a mutation in an MMR gene.6

Table 2. Bethesda Guidelines for Testing Colorectal Tumors for Microsatellite Instability (MSI)6,20

Colorectal tumors should be tested for MSI in individuals meeting any of the following:

  • CRC diagnosed at age <50 years
  • Presence of synchronous CRC, metachronous CRC, or other Lynch syndrome-associated tumorsa, regardless of age
  • CRC with the MSI-H histologyb diagnosed at age <60 years
  • CRC with ≥1 first-degree relative with a Lynch syndrome-related tumor with 1 of the cancers diagnosed at age <50 years
  • CRC with  ≥2 first- or second-degree relatives with Lynch syndrome-related tumors, regardless of age

CRC, colorectal cancer.


Endometrial, stomach, ovarian, pancreas, ureter and renal pelvis, biliary tract, and brain tumors; sebaceous gland adenomas and keratoacanthomas as seen in Muir-Torre syndrome; and carcinoma of the small bowel.


Presence of tumor infiltrating lymphocytes, Crohn-like lymphocytic reaction, mucinous/signet-ring differentiation, or medullary growth pattern.

Table 3. Amsterdam II Criteria for Identifying Families with Lynch Syndrome21

≥3 relatives with a Lynch syndrome-associated tumora
  • 1 is a first-degree relative of the other 2
  • ≥2 successive generations affected
  • ≥1 diagnosed at <50 years of age
  • FAP should be excluded in the patients with CRC
  • Tumor should be verified by pathologic examination

FAP, familial adenomatous polyposis.
a Cancer of the colon, endometrium, small bowel, ureter, or renal-pelvis.

Test Availability [return to contents]

The tests recommended by the NCCN and others include screening tests such as MSI and IHC of the 4 MMR proteins (supplemented by BRAF mutation testing) as well as germline mutation testing of the MMR genes. These tests are offered by Quest Diagnostics and can be ordered using the test codes listed in Table 4. The table is provided for informational purposes only and is not intended as medical advice. A physician's test selection and interpretation, diagnosis, and patient management decisions should be based on his/her education, clinical expertise, and assessment of the patient.

Table 4. Tests Available for Diagnosis and Management of Lynch Syndrome

Test Code


Test Name

Clinical Use

Tissue Testing




BRAF Mutation Analysisb

Rule out Lynch syndrome in people with loss of MLH1 IHC staining on colorectal cancer tissuec

91332 (91333)

88342 x4

Lynch Syndrome Tumor Panel, IHC with (or without) Interpretationc

Includes MLH1 (70196 or 16967), MSH2 (70197 or 16971), MSH6 (16938 or 16252), and PMS2 (16997 or 16254) protein expression.

Screen for Lynch syndrome in patients with colorectal or endometrial cancer

Identify MMR gene(s) for mutation testing



Microsatellite Instability (MSI), HNPCCb

Screen for Lynch syndrome in patients with colorectal or endometrial cancer


Varies with complexity of case

Tissue, Gastrointestinal Pathology Report

Histopathologic diagnosis of  CRC

Whole Blood (Mutation) Testing



81292, 81294

Lynch Syndrome, MLH1 Sequencing and Deletion/Duplicationb

Confirm diagnosis of Lynch syndrome in patients with 1) loss of MLH1 staining and negative BRAF test and/or 2) loss of PMS2 staining


81295, 81297, 81403

Lynch Syndrome, MSH2 Sequencing and Deletion/Duplication (Including EPCAM)b

Confirm diagnosis of Lynch syndrome in patients with 1) loss of MSH2 staining and/or 2) loss of MSH6 staining


81298, 81300

Lynch Syndrome, MSH6 Sequencing and Deletion/Duplicationb

Confirm diagnosis of Lynch syndrome in patients with 1) loss of MSH6 staining and/or 2) loss of MSH2 staining


81292, 81295, 81297, 81298, 81317, 81294, 81300, 81319, 81403

Lynch Syndrome Panelb

Includes detection of point mutations, deletions, and duplications in MLH1, MSH2, MSH6, and PMS2 genes and testing for 3′-EPCAM deletion.

Confirm diagnosis of Lynch syndrome in patients with colorectal or endometrial cancer and MSI high/IHC normal (all MMR proteins expressed) test results

Assess risk of Lynch syndrome in patients with a Lynch syndrome-related tumor and no previous tumor tissue testing

Assess risk of Lynch syndrome in at-risk family members when familial mutation is unknown


81317, 81319

Lynch Syndrome, PMS2 Sequencing and Deletion/Duplicationb

Confirm diagnosis of Lynch syndrome in patients with 1) loss of PMS2 staining and/or 2) loss of MLH1 staining


81318, 81293, 81296, 81299

MyVantage™, Single Siteb

Submission of specific family mutation is required.

Assess risk of Lynch syndrome in at-risk family members when the family mutation is known in PMS2, MLH1, MSH2, or MSH6

IHC, immunohistochemical testing; MMR, mismatch repair; CRC, colorectal cancer.


The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.


This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the U.S. Food and Drug Administration. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.


In rare cases, a patient with Lynch syndrome may have a BRAF-positive result.22,23 Consider germline testing if the patient is young at disease onset or has significant family history.6

Test Selection and Interpretation [return to contents]

Individuals with Lynch Syndrome-related Cancer

MSI and/or IHC testing of tumor tissue is used to identify patients who may benefit from MMR mutation testing, which is required for a Lynch syndrome diagnosis.6,24 In patients fulfilling the Bethesda guidelines (Table 2), MSI and IHC screening tests were both found to be effective in selecting patients for MMR mutation testing.4,6,25 However, using either MSI or IHC testing alone resulted in false-negative results.26 Thus, sensitivity can be maximized by using both MSI and IHC testing.6,27

If there is insufficient or no tumor available, testing can begin directly with MMR gene testing using whole blood.6 These approaches are demonstrated in Figure 1.

Figure 1. Suggested Laboratory Testing for the Diagnosis of Lynch Syndrome

Microsatellite Instability (MSI) Testing

MSI testing compares the number of nucleotide repeats in microsatellite markers with the number in normal tissue (or whole blood) from the same individual. If the number differs, MSI is present. Results are reported as MSI-high (MSI-H) if ≥2 of the 5 National Cancer Institute-recommended markers show instability. 20 MSI-low (MSI-L) results are reported if 1 of 5 is positive; negative results are reported as microsatellite stable (MSS). Although an MSI-H result is the hallmark of Lynch syndrome, it is also found in 10% to 15% of sporadic CRC cases. 28 As such, an MSI-H result requires follow-up with MMR gene mutation testing. In families with a strong suspicion of Lynch syndrome, MMR gene mutation testing should be considered regardless of MSI status, since MSI results do not rule out Lynch syndrome.20

Immunohistochemical (IHC) Testing for MMR Proteins

A pathogenic variant in an MMR gene(s) usually leads to a loss of corresponding protein expression, which can be detected using IHC testing.  The absence of IHC staining thus serves as a surrogate marker of an MMR pathogenic variant. IHC testing is usually followed with genetic testing of selected MMR genes to determine whether a deleterious mutation is present. For example, loss of MSH2 expression is confirmed with MSH2/EPCAM mutation testing. The overall clinical sensitivity (Lynch syndrome detection rate) of IHC MMR protein testing of colorectal cancers is 77% (95% CI, 69% to 84%).29

MMR Gene Mutation Testing

Germline mutation testing should include analysis for various types of DNA alterations. DNA sequence changes, such as point mutations and alterations involving just a few nucleotides, are most frequent. However, roughly 17% of individuals with suspected Lynch syndrome have large rearrangements, which may include deletions and duplications involving partial, whole, or multiple gene exons.30 Approximately 32% of the mutations occur in MLH1, 39% in MSH2, 14% in MSH6, and 15% in PMS2.29

Selection of the MMR gene(s) to be analyzed can be based on the pattern of IHC staining, ie, which proteins stain negative. Four patterns constitute 98% of the IHC tumor-screening results31 and each is followed with a different mutation-testing approach (Figure 2).

Figure 2. Suggested Laboratory Testing for the Diagnosis of Lynch Syndrome in Patients Who Have Abnormal IHC Results

Loss of Both MLH1 and PMS2 Staining

This is the most common IHC pattern.31 In most cases, it is associated with non-Lynch syndrome CRC and is primarily caused by MLH1 promoter methylation and silencing of the MLH1 gene. MLH1 loss usually results in degradation and loss of PMS2, which is unstable outside of an MLH1/PMS2 heterodimeric complex.

Since BRAF V600E mutation is the primary cause of MLH1 promoter methylation,32 loss of MLH1 and PMS2 staining should be followed with BRAF mutation testing. A positive BRAF V600E result essentially rules out Lynch syndrome.19 Note that BRAF mutation testing is appropriate only for patients with CRC since the mutation is uncommon in other Lynch syndrome-associated cancers.5,6 For the other types of cancers, proceed directly to MLH1 gene testing.

When a BRAF V600E test result is negative, Lynch syndrome is likely. MLH1 and PMS2 gene mutation testing is suggested. Testing may be performed concurrently; however, since a pathogenic variant in MLH1 is much more likely than in PMS2, PMS2 mutation testing could be performed sequentially (ie, after a negative MLH1 test).

Loss of Both MSH2 and MSH6 Staining

This is the second most common IHC pattern.31 MSH2 and MSH6 also form a heterodimeric complex. MSH6 is unstable outside this complex, so loss of MSH2 usually results in degradation and loss of MSH6. Loss of these 2 proteins should be followed with MSH2 mutation testing. MSH2 gene testing offered by Quest Diagnostics includes testing for a 3′-deletion in the EPCAM gene, which occurs in about 1% to 3% of Lynch syndrome cases.5,33 The EPCAM gene is adjacent to the MSH2 gene in the genome. Mutation of the 3' end of EPCAM can influence MSH2 gene expression. When present, a 3′-deletion in EPCAM inactivates the MSH2 gene.34 Thus, loss of MSH2 staining can be explained either by MSH2 mutation or by 3′-deletion in EPCAM. The presence of either is diagnostic of Lynch syndrome. Testing for an MSH6 mutation should be considered as well. It can be performed along with the MSH2/EPCAM mutation test or after a negative MSH2/EPCAM test.

Loss of MSH6 Only

This is the third most common pattern,31 most likely due to a mutation in the MSH6 gene.35 A deleterious mutation in either the MSH6 or the MSH2 gene, however, is a plausible etiology. Sequential or concurrent MSH6 and MSH2 mutation testing can thus be considered.6 Loss of MSH6 staining should be interpreted with caution in rectal cancers, as it may be caused by neoadjuvant chemoradiotherapy.6 

Loss of PMS2 Only

This is the fourth most common pattern,31 most likely due to a mutation in the PMS2 gene.36 A deleterious mutation in either the PMS2 or the MLH1 gene is a plausible etiology. Sequential or concurrent testing for both PMS2 and MLH1 mutation may be considered for this pattern.6

Other Patterns

These are rarely observed, and the mechanisms responsible are not always understood.31,37 Loss of staining for a particular MMR protein, however, should generally be followed by mutation testing of the corresponding gene and possibly its heterodimeric partner.6

Detection of a deleterious MMR gene mutation is diagnostic for Lynch syndrome, but failure to identify a mutation does not rule out the diagnosis.5

Unaffected Family Members at Risk for Lynch Syndrome

MMR gene mutation testing is recommended for at-risk individuals. These include blood relatives of Lynch syndrome patients and individuals who meet the Amsterdam criteria (Table 3) or who have a ≥5% risk for Lynch syndrome based on computer models (MMRPro, PREMM[1,2,6], or MMRpredict). When the family pathogenic variant is known, a targeted, gene-specific test that can detect the specific alteration can be used (eg, MyVantage™, Single Site, test code 93945). When the family mutation is not known, the Lynch Syndrome Panel (test code 91461) can be used; this panel offers comprehensive MMR gene testing. When using this panel, relatives with a Lynch syndrome-related cancer should be tested before relatives without cancer in order for test results to be most informative.6 Because not all Lynch syndrome families meet the Amsterdam criteria, the panel should also be considered when there is a strong suspicion of Lynch syndrome based on family history.6 Figure 3 demonstrates these options.

Figure 3. Risk Assessment of Family Members at Risk for Lynch Syndrome

Identification of a deleterious mutation in an MMR gene confirms the clinical diagnosis of Lynch syndrome and thereby identifies individuals who may benefit from risk reduction or routine surveillance procedures. According to NCCN guidelines, CRC surveillance should be initiated at 20 to 25 years of age or 2 to 5 years earlier than the youngest age at which CRC was diagnosed in the family (whichever is earlier).6 Surveillance for other Lynch syndrome-related cancers varies; more information can be found in the NCCN guidelines.

Gene testing should precede surveillance to ensure proper patient management. If genetic testing is negative for the known pathogenic variant, cancer screening can likely be performed as for the average-risk population.

Additional assistance in test selection and interpretation of results is available from Quest Diagnostics Genomics Client Services by calling 866.GENE.INFO (866.436.3463).

References [return to contents]

  1. Cancer facts and figures 2016. American Cancer Society Website. http://www.cancer.org/acs/groups/content/
    . Accessed January 15, 2016.

  2. National Cancer Institute. Genetics of colorectal cancer (PDQ®). Available at: http://www.cancer.gov
    . Updated February 12, 2016, Accessed March 15, 2016.

  3. Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med. 2003;348:919-932.

  4. Funkhouser WK, Jr., Lubin IM, Monzon FA, et al. Relevance, pathogenesis, and testing algorithm for mismatch repair-defective colorectal carcinomas: a report of the Association for Molecular Pathology. J Mol Diagn. 2012;14:91-103.

  5. Kohlmann W, Gruber SB. Lynch syndrome. In: Pagon RA, Adam MP, Ardinger HH, et al., eds. GeneReviews® [Internet]. Seattle, WA; University of Washington, Seattle; 1993-2016 http://www.ncbi.nlm.nih.gov/books/NBK1211/. Updated May 22, 2014, Accessed February, 29 2016.

  6. National comprehensive cancer network clinical practice guidelines in oncology (NCCN Guidelines®). Genetic/familial high-risk assessment: colorectal version1.2016. http://www.nccn.org. Updated July 8, 2016. Accessed July 14, 2016.

  7. Kastrinos F, Mukherjee B, Tayob N, et al. Risk of pancreatic cancer in families with Lynch syndrome. JAMA. 2009;302:1790-1795.

  8. Barrow E, Alduaij W, Robinson L, et al. Colorectal cancer in HNPCC: cumulative lifetime incidence, survival and tumour distribution. A report of 121 families with proven mutations. Clin Genet. 2008;74:233-242.

  9. Bonadona V, Bonaiti B, Olschwang S, et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA. 2011;305:2304-2310.

  10. Choi YH, Cotterchio M, McKeown-Eyssen G, et al. Penetrance of colorectal cancer among MLH1/MSH2 carriers participating in the colorectal cancer familial registry in Ontario. Hered Cancer Clin Pract. 2009;7:14.

  11. Dowty JG, Win AK, Buchanan DD, et al. Cancer risks for MLH1 and MSH2 mutation carriers. Hum Mutat. 2013;34:490-497.

  12. Moller P, Seppala T, Bernstein I, et al. Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database. Gut. 2015

  13. Ramsoekh D, Wagner A, van Leerdam ME, et al. Cancer risk in MLH1, MSH2 and MSH6 mutation carriers; different risk profiles may influence clinical management. Hered Cancer Clin Pract. 2009;7:17.

  14. van der Post RS, Kiemeney LA, Ligtenberg MJ, et al. Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers. J Med Genet. 2010;47:464-470.

  15. Vasen HF, Stormorken A, Menko FH, et al. MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families. J Clin Oncol. 2001;19:4074-4080.

  16. Renkonen-Sinisalo L, Aarnio M, Mecklin JP, et al. Surveillance improves survival of colorectal cancer in patients with hereditary nonpolyposis colorectal cancer. Cancer Detect Prev. 2000;24:137-142.

  17. Jarvinen HJ, Aarnio M, Mustonen H, et al. Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology. 2000;118:829-834.

  18. Giardiello FM, Allen JI, Axilbund JE, et al. Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US multi-society task force on colorectal cancer. Am J Gastroenterol. 2014;109:1159-1179.

  19. Domingo E, Laiho P, Ollikainen M, et al. BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing. J Med Genet. 2004;41:664-668.

  20. Umar A, Boland CR, Terdiman JP, et al. Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96:261-268.

  21. Vasen HF, Watson P, Mecklin JP, et al. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology. 1999;116:1453-1456.

  22. Wang L, Cunningham JM, Winters JL, et al. BRAF mutations in colon cancer are not likely attributable to defective DNA mismatch repair. Cancer Res. 2003;63:5209-5212.

  23. Ward RL, Dobbins T, Lindor NM, et al. Identification of constitutional MLH1 epimutations and promoter variants in colorectal cancer patients from the Colon Cancer Family Registry. Genet Med. 2013;15:25-35.

  24. Evaluation of Genomic Applications in Practice Prevention Working Group. Recommendations from the EGAPP working group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives. Genet Med. 2009;11:35-41.

  25. Pinol V, Castells A, Andreu M, et al. Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer. JAMA. 2005;293:1986-1994.

  26. Lagerstedt Robinson K, Liu T, Vandrovcova J, et al. Lynch syndrome (hereditary nonpolyposis colorectal cancer) diagnostics. J Natl Cancer Inst. 2007;99:291-299.

  27. Pino MS, Chung DC. Application of molecular diagnostics for the detection of Lynch syndrome. Expert Rev Mol Diagn. 2010;10:651-665.

  28. Power DG, Gloglowski E, Lipkin SM. Clinical genetics of hereditary colorectal cancer. Hematol Oncol Clin North Am. 2010;24:837-859.

  29. Palomaki GE, McClain MR, Melillo S, et al. EGAPP supplementary evidence review: DNA testing strategies aimed at reducing morbidity and mortality from Lynch syndrome. Genet Med. 2009;11:42-65.

  30. Mancini-DiNardo D, Judkins T, Woolstenhulme N, et al. Design and validation of an oligonucleotide microarray for the detection of genomic rearrangements associated with common hereditary cancer syndromes. J Exp Clin Cancer Res. 2014;33:74.

  31. Yuan L, Chi Y, Chen W, et al. Immunohistochemistry and microsatellite instability analysis in molecular subtyping of colorectal carcinoma based on mismatch repair competency. Int J Clin Exp Med. 2015;8:20988-21000.

  32. Parsons MT, Buchanan DD, Thompson B, et al. Correlation of tumour BRAF mutations and MLH1 methylation with germline mismatch repair (MMR) gene mutation status: a literature review assessing utility of tumour features for MMR variant classification. J Med Genet. 2012;49:151-157.

  33. Landon M, Saam J, Brown KL, et al. Lynch syndrome patients with limited family history identified in a laboratory setting: a descriptive study. Oncology. 2015;89:221-226.

  34. Kempers MJ, Kuiper RP, Ockeloen CW, et al. Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: a cohort study. Lancet Oncol. 2011;12:49-55.

  35. Southey MC, Jenkins MA, Mead L, et al. Use of molecular tumor characteristics to prioritize mismatch repair gene testing in early-onset colorectal cancer. J Clin Oncol. 2005;23:6524-6532.

  36. Senter L, Clendenning M, Sotamaa K, et al. The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology. 2008;135:419-428.

  37. Hall G, Clarkson A, Shi A, et al. Immunohistochemistry for PMS2 and MSH6 alone can replace a four antibody panel for mismatch repair deficiency screening in colorectal adenocarcinoma. Pathology. 2010;42:409-413.

Content reviewed 11/2016


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* The tests listed by specialist are a select group of tests offered. For a complete list of Quest Diagnostics tests, please refer to our Directory of Services.