Colorectal cancer: pathology

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1 UK NEQAS for Molecular Pathology Colorectal cancer: pathology Nick West Pathology & Tumour Biology May 2013

2 Colorectal cancer (CRC) 40,695 new cases in ,708 deaths

3 Management of CRC Surgery Main curative process 4% mortality 40-90% survival depending stage Screening

4 Management of CRC Oncology Some additional survival benefit Greater if can predict response Chemotherapy Radiotherapy

5 Pathology in CRC

6 Pathology in CRC

7

8 Pathology in CRC At least 5 blocks of tumour and 1 normal

9 Pathology in CRC

10 Pre-operative therapy No evidence of response Good response

11 Good pathology saves lives! Feedback to surgeon Prognosis, completeness of excision (CRM involvement), plane of surgery Feedback to radiologist Accuracy of staging, predicted completeness of excision Feedback to oncologist Effectiveness of neoadjuvant therapy, need for adjuvant therapy (stage III, high risk stage II), KRAS testing

12 Good pathology saves lives! Pathology Screening Influencing the quality of surgery

13 The cost of CRC care Per patient Pathology 200 Radiology 400 Surgery 6,631 to 6,891 Chemotherapy 500 to 125,000 Yu-Ning Wong et al ASCO 2006

14 The cost of CRC care Tumour factors - Stage - Grade Stroma - Pattern of invasiveness - Peritoneal involvement - Lymphatic/vascular/ neural invasion - Perforation - Proliferation Host factors - Immune response Treatment factors - Response to treatment - Completeness of removal - Plane of surgery Molecular factors - Mutations - dmmr - RNA profiles??? 150-2,000

15 What additional tests should we use? Increasing evidence Deficient mismatch repair (prognosis, metachronous cancers, HNPCC) KRAS mutations BRAF mutations Questionable value OncotypeDx colon (HR 1.5) Unknown Expression arrays CGH and copy number variation tests Proteomics HR 1.46

16 New prognostic tests Valuable if they change therapy Good prognosis (no need for therapy) Poor prognosis (pre- or post-operative adjuvant therapy to reduce recurrence risk) Must add value to current standard histopathology! Must be tested and validated in comparison to quality assured pathology

17 Deficient mismatch repair n =1913

18 KRAS & BRAF mutations dmmr and BRAF wild type high risk HNPCC Recurrence by KRAS 12,13,61 Recurrence BRAF HR = ( )

19 Prediction of response Site % KRAS 12 &13 40 KRAS 61 3 KRAS NRAS 12,13 & 61 3 BRAF KRAS mutants KRAS wild type

20 Difficult areas Take sufficient tumour blocks Heterogeneity Around 10% Reduce by using sections from all tumour blocks vs. only one block After treatment Biopsies are small!

21 Colorectal cancer clinical trials

22 Pathology involvement in trials MRC FOCUS 3 Feasibility MRC FOCUS 4 First large prospective trial

23 Pathology in 2013

24 Three dimensional pathology

25

26 Radiology & pathology integration

27 Summary Colorectal cancer is a common disease High quality pathology is essential Evidence for molecular tests increasing MMR, KRAS, BRAF New tests must add value and be tested against gold standard pathology Some areas are difficult Heterogeneity, amount of tumour (biopsies, post-treatment) The future is very exciting!

28 Acknowledgements Pathological Society Academy of Medical Sciences Yorkshire Cancer Research National Institute for Health Research Phil Quirke & team

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