Reports From the Field

Screening for Lynch Syndrome Among Patients with Colorectal Cancer: Experiences from a Multihospital Health System



From the Hartford HealthCare Cancer Institute, Hartford, CT (Dr. Salner and Dr. Yu), and the Albert Einstein College of Medicine, New York, NY (Mr. Sekerak).


  • Objective: To explore the extent to which patients with newly diagnosed colorectal cancer (CRC) received standard of care screening for Lynch syndrome (LS), with testing of specimens for loss of expression of mismatch repair (MMR) genes and referral of patients with positive results to a genetic counselor.
  • Methods: We conducted a retrospective study using cancer registry data from the Hartford HealthCare Cancer Institute, which is part of a 5-hospital urban health care system. Measures that were included in this study were patient age and gender, date of surgery, pathologic grade, pathologic stage, presence of MMR immunohistochemical test, and presence of genetic counseling and testing for MMR-positive patients
  • Results: 432 patients diagnosed with CRC during calendar years 2014 and 2015 were identified. The average age of the patients was 68.2 years and overall 81.3% of patients were screened (range, 30.8%–94.5%). Of the patients with MMR-positive results, 15 (57.7%) received a genetic consult and 10 of these had a germline test. Seven patients (70%) tested positive for LS. Patients who were diagnosed with LS were younger, and the majority were male.
  • Conclusion: This study showed that improved implementation strategies for LS screening at HHC hospitals were needed, as MMR testing was not fully implemented across all of our sites. Strategies that led to improved compliance included consensus building, comprehensive communications, embedding the new standard in a series of steps, and subsequent audits with feedback.

Keywords: Lynch syndrome; colorectal cancer; quality; screening; standard of care.

Colorectal cancer (CRC) is the third most common cancer in men and women, accounting for as many as 135,000 new cases and 50,000 cancer deaths per year in the United States.1 These cancers appear to be heterogeneous with multiple molecular subtypes, including chromosomal instability and microsatellite instability (MSI) pathways.2,3 MSI tumors may result from sporadic mutations or constitutional mutations. Lynch syndrome (LS), formerly known as hereditary non-polyposis colorectal cancer, is caused by a germline mutation in 1 of several DNA mismatch repair (MMR) genes or loss of expression of MSH2 due to deletions in the EPCAM gene.4 The MMR genes that have been identified in LS are MLH1, MSH2, MSH6, and PMS2.5-8 The protein products of these genes are essential to maintaining the integrity of the DNA sequence. Importantly for clinical practice, patients who carry gene mutations indicative of LS have a higher risk of certain cancers, namely CRC, pancreatic cancer, and endometrial cancer, among others.8,9

While most occurrences of CRC are sporadic, accounting for roughly 90% of all cases, approximately 5% to 10% of CRCs are caused by inherited genes.10 LS is the most common cause of inherited CRC, accounting for 1% to 3% of all CRC cases.8,10,11 Individuals with LS are likely to have onset of disease at an earlier age and also have a much higher risk for developing CRC, with a lifetime risk of CRC of approximately 70% for men and 45% for women.12,13 Thus, it is important to identify patients who have LS so that they can receive proper surveillance and care (ie, frequency of follow-up and treatment options). It is additionally important for family members of patients with LS to receive proper genetic counseling and genetic testing to better understand their possible predisposition and risk for CRC. CRC screening for LS helps clinicians appropriately personalize patient care, as the adjuvant therapy selection may be influenced by MMR results.3

The National Comprehensive Cancer Network guidelines recommend screening all patients with newly diagnosed CRC for Lynch syndrome. Hartford HealthCare (HHC), a large health care system located in Hartford, CT, has adopted these guidelines at the 5 hospitals within its cancer institute. According to the standard of care, a positive MMR pathology report should result in a referral to a genetic counselor for consultation, and the genetic counselor would recommend genetic testing for germline MMR genes. This quality improvement project sought to evaluate the performance of each of the 5 hospitals in implementing the standard of care for screening for LS in patients with CRC and to determine if the appropriate genetic referrals were made for patients with positive screening results. This study focused on LS screening in patients diagnosed only with CRC.

Data Collection and Analysis

We conducted a retrospective study examining all cases of patients diagnosed with invasive colon or rectal cancer at each of the 5 HHC Cancer Institute hospitals during calendar years 2014 and 2015. The study was developed as a quality improvement project for the HHC cancer centers. The database of patients diagnosed with colon and rectal cancer at HHC was obtained from our cancer registry.

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