Lynch Syndrome screening by antibody alone — ASN Events
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Lynch Syndrome screening by antibody alone (#129)

Tamarind Hamwood 1 2 , Adrienne Morey 3 , Robyn Levingston 4 , Veli Marjoniemi 5 , Elizabeth Salisbury 6 , Leon Vonthethoff 5 , Nicholas J Hawkins 7
  1. POW Clinical School, UNSW Australia, Sydney, NSW, Australia
  2. Translational Cancer Research Network, Sydney, NSW, Australia
  3. Anatomical Pathology, SydPath, Sydney, NSW, Australia
  4. Douglass Hanly Moir, North Ryde, NSW, Australia
  5. Anatomical Pathology, SEALS Central, Kogarah, NSW, Australia
  6. Anatomical Pathology, SEALS North, Randwick, NSW, Australia
  7. UNSW Australia, Sydney, NSW, Australia

Aims: Identifying cases of Lynch syndrome (LS) amongst apparently sporadic colorectal cancers is an important health goal, but family history is often insufficient. Routine immunohistochemical (IHC) detection of mismatch repair enzyme loss (MMRD) by pathologists is an important first step, but is confounded by the large number of MLH1-negative sporadic cases in this category. Additional molecular assessment for BRAF V600E mutation adds greater specificity to screening protocols, but does not fit with normal laboratory workflows. In this study, we evaluated the utility of IHC for mutant BRAF as an adjunct to MMRD IHC in detecting high-likelihood cases of LS.

 Methods: A BRAF IHC assay protocol was developed and transferred to four pathology laboratories in Sydney. After training, six pathologists separately assessed an experimental cohort of 117 clinically relevant (MMRD) samples of known microsatellite, BRAF mutation and LS germline status.

Results: All laboratories were able to perform the assay successfully, and all pathologists could interpret the results reliably after training. Improvement in interpretation was evident after communal discussion of cases. The sensitivity (49% - 98%) and specificity (86% - 100%) for detecting BRAF V600E varied amongst individual pathologist, although the consensus call on all cases was 100% specific. These values are acceptable given the purpose of the assay.

Conclusions: IHC assessment of BRAF mutation status in colorectal cancer is reliable and reproducible. In conjunction with MMR IHC, it allowed a six-fold reduction by the number of cases of potential LS requiring triage at a family cancer clinic (FCC). Variation in results was mostly due to different interpretation between pathologists, highlighting the importance of training and the provision of educational resources to support implementation of this new assay. 

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