1. Genetics and Pathology What can they do for each other? Scottish Association of Histotechnology; Friday 27 th May 2011

2. National Initiatives Affecting Both Disciplines

3. Nationally funded NHS Genetic Services Four centre Consortium covering service Genetics for Scotland Responsible for a wide range of inherited genetic conditions Scottish Genetic Laboratory Consortium

4. Future workload of Genetics will increasingly be Molecular Pathology/Diagnostic tests Changes at the chromosome and DNA level will –Aid diagnosis –Determine outcome –Define treatment pathways Partnership with Pathology is crucial for effective delivery of Molecular Diagnostic tests Excellent relationship between Pathology and Genetics in Tayside Genetics and Pathology in NHS Tayside

5. Pathology Sample

6. The starting point for all Molecular tests is DNA Yield is 1.1  g (20  l at 55ng/  l) 2x10  m

8. A good example of how Genetics and Pathology can work together for inherited cancer is Lynch syndrome Familial colorectal cancer syndrome characterised by hundreds of colorectal polyps as well as extra-colonic tumours Important to distinguish families at high risk of Lynch syndrome from sporadic disease Done through combination of genetic techniques and IHC on tumour sections. Allows targeted testing of tumours for MMR defects

9. “Best approach for identifying cases of Lynch syndrome is for Pathologists and Geneticists to work closely together” “MSI and IHC were most cost effective when used as an initial screening strategy”

10. Diagnostic testing – HNPCC and MSI Medium Risk MSI + IHC

11. NR -21 BAT- 26 BAT- 25 NR- 24 MONO -27 MSI+ / MHLH neg

12. Diagnostic testing – HNPCC and MSI

13. Genetics and Sporadic Cancer “Not all cancer is inherited but all cancer is genetic” Diagnostic IgH & TCR gene rearrangements MSI BRAF p.V600E Prognostic KRAS cKIT / PDGFR Her2

14. Prognostic testing – KRAS and cKIT/PDGFRA The presence of a mutation in KRAS in colorectal cancer or a cKIT / PDGFRA mutation in GIST can have significant implications for treatment. KRAS Approximately 30-50% of colorectal tumours have a mutation at 3 codons in gene Tumours with a mutation will not respond to a specific class of treatment Important for patients to know what the mutation status of their tumour is GIST 85-90% of GISTs have activating mutations in cKIT or PDGFRA The position of the mutation can influence how the tumour will respond to specific treatment.

16. KRAS

17. For KRAS testing crucial to get good quality tissue sections and to know the tumour load

18. GIST

19. What can be gained by working together? Shared expertise, skills and capital equipment Opportunities for integrated training at various career levels Opportunity to develop specialist teams Shared R&D Collaborative working is only way of delivering Molecular Pathology/Diagnostics Future proof both disciplines Ultimately provide the best service to patients.

20. New initiatives in Scotland Training in Molecular Pathology/Diagnostics funded by NES Molecular Pathology Consortium

22. The Future for Genetics and Pathology

23. THANKS Everyone in Pathology at Ninewells Hospital