Molecular testing strategies for Lynch syndrome in people with colorectal cancer

Oxford University Hospitals NHS Foundation Trust

The Oxford Department of Clinical Genetics and Genomics has 14 full- or part-time genetic counsellors who see people with, or at risk of, hereditary forms of cancer as well as people with, or at risk of, other genetic conditions. There are also 2.2 full-time equivalent cancer genetics consultants.

In 2014, the trust started to routinely test all CRCs managed surgically using immunohistochemistry (IHC) to identify mismatch repair deficiency. This decision was made by the Oxford Mismatch Repair group to avoid unnecessary delays and the need for pathological reassessment because most tumours were already being tested. Membership of the group includes the local genetics, oncology, gastroenterology and laboratory teams. This new approach was named the 'MMR management protocol'.

Before the new protocol was adopted, CRCs from people under 50 years were automatically being tested using MMR testing, in line with the Royal College of Pathology dataset for CRC histopathology reports. Approval for this test request was gained at the colorectal multidisciplinary team meeting (MDT). CRCs in people over 50 years were only tested if requested by the oncology service.

The trust carried out 256 primary CRC resections in the 12 months before implementing the new protocol:

IHC testing is carried out within the hospital's histopathology laboratory, at the time of (or very shortly after) surgery. This means that results are reported to the oncology team within 10 days of surgery. This has saved time and money because tumour sample blocks no longer need to be retrieved from storage for retrospective testing.

If the IHC test result suggests loss of any of the MMR proteins (abnormal result), the pathology report recommends that the patient is referred to the clinical genetics services for review and the tumour sample and copy of the IHC report is sent to the molecular genetics laboratory. During the clinical genetics appointment, the person's family history is explored and the appropriate further molecular genetics tests are requested.

In the 12 months before adoption of the MMR management protocol, only 30% of people whose CRC had MMR deficiency were referred to clinical genetics services. After adoption of the protocol, all the people aged under 70 with CRCs identified as having MMR deficiency have been either referred directly to clinical genetics services, or informed of the need to consider this when their ongoing treatment is complete. The genetics team has spent 2 years working with pathology staff to ensure this change is implemented. Despite this, referrals to clinical genetics services for people over 70 still varies and this is dependent upon clinical judgement. The management protocol is supported by an information pack that includes a patient information resource, pro forma referral letter, guidance flow chart and referral criteria (see developing local documentation).

In Oxford, a strong collaboration between the cancer MDT, histopathology, genetics laboratories, and clinical genetics departments was necessary to develop and optimise the pathways for these patients. Implementation of plans for the centralisation of molecular diagnostic laboratory services in England as outlined in Building On Our Inheritance: Genomic Technology in Healthcare needs to ensure that these close relationships remain.