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The Issue of Tissue - Cancer Banking for Research. Dr Gerry Thomas South West Wales Cancer Institute, Swansea. Why set up a tissue bank?. Development of a cancer depends on the acquisition of a number of growth control defects within a clone of cells.

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The Issue of Tissue -

Cancer Banking for Research

Dr Gerry Thomas

South West Wales Cancer Institute, Swansea


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Why set up a tissue bank?

  • Development of a cancer depends on the acquisition of a number of growth control defects within a clone of cells

  • The ability to pool information on a number of different molecular changes should provide a better insight into the process of carcinogenesis

  • The quality of the molecular biological data generated depends on the quality of the material used and above all on pathological diagnosis

  • Avoids competition and fosters collaboration


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Why make use of a tissue bank?

  • Issues of consent from patients

  • Material is collected in a uniform way to written protocols

  • Can use high throughput methods to screen large numbers of samples

  • Can link biological results to clinical presentation and outcome or to response to therapy


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High Throughput

Expression microarrays

Mass Spectroscopy

Tissue Microarray

Validation of targets

Candidate biomarkers

Clinical Trials using Biomarkers to direct therapy

Role of Tissue Banking in Cancer Research

Clinical Database

Clinical Trials

Tissue Bank


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Ethics

  • The interests of the patient must come first, but equally it is unethical not to use material surplus to diagnostic requirements to benefit other patients in the future

  • Informed consent should be obtained whenever practical - certainly for prospective collections.

  • Level of consent offered to the donor should reflect the degree of risk to the patient


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More Ethics - labelling of samples

  • Directly identifiable - the researcher knows the identify of the donor

  • Indirectly identifiable - sample is coded, identity of donor unknown to the researcher, but can be retrieved by the provider of the tissue

  • Fully anonymised - at least extremely difficult, if not impossible to identify the donor


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What do the patients think?

Review of the Peterborough NHS tissue bank

  • Time period: 01.10.98 to 30.09.02

  • 3140 interviews, 38 refusals

  • No single reason - varied from cultural/language difficulties (most common - 4 cases) to wishing to “keep” their tissue.

  • Despite the fact that the patients were informed would be used by pharmaceutical industry (i.e. commercial use) only 2 patients were against commercial involvement

Jack AL, Womack C (2003) BMJ 327: 262


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What type of biospecimens should be collected?

  • Serum/plasma samples can be used to study protein markers of disease

  • Blood samples to extract DNA to look for germline polymorphisms

  • Pairs of samples from frozen tumour and normal tissue – can look at expression of protein and RNA, and DNA alterations

  • Paraffin blocks for studies involving localisation of proteins and mRNA to different cell types


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What type of data should be collected?

  • Standard information – age, sex, family history

  • Detailed pathology information – subtype of tumour, stage/grade of disease, clinical markers

  • Type of treatment (radiation/chemotherapy)

  • Toxicity (if possible)

  • Outcome of treatment – relapse when and where


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+T

100

8040

8353

+AG

8673

50

0

Use of frozen material

  • single gene studies, either by RT-PCR, PCR


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ER

PgR

mcm2

Ki67

Her2

T

N

T

N

T

N

T

293

NPA

  • tissue microarrays – immunocytochemistry, in situ hybridisation and FISH

Use of paraffin material

  • single gene studies, either by PCR, ISH, FISH, immunocytochemistry


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Importance of QA

  • Good quality research depends on good quality material

  • Material must be what it says it is on the pot – i.e. needs to be pathologically reviewed

  • Must be fit for purpose – needs to be handled correctly and stored correctly

  • Should be agreed SOPs that are adhered to



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TC

C

Effect of method of storage on serum proteomics

Villanueva et al., 2005

J Proteome Res 4: 1060-1072


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Recommendations for QA

  • SOPs should be written and adhered to – if protocol changed, check quality equal or improved

  • If you cannot control input (i.e. alter surgical practice etc) must assess quality at all stages – from pathology to extracted material

  • QA procedures must reflect the use to which material will be put – talk to your researchers!


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  • Similar quality standards should be applied to paraffin embedded material as to frozen material

  • When you are using bioinformatics to combine studies from a number of different sources, must also have detailed QA to ensure that research studies have been conducted satisfactorily


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Access to tissue banks means that we can ask more intelligent questions, through being able to access large numbers of samples with multiple variants, or select highly matched patient groups from a larger cohort.


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How can we better analyse research data from tissue banks? intelligent questions, through being able to access large numbers of samples with multiple variants, or select highly matched patient groups from a larger cohort.

  • Develop Bioinformatics to enable us to combine data from research studies with clinical information

  • Use computer models to define biomarker profiles that enable us to better diagnose different subtypes of cancer and to decide which patient should be given which therapy (and in which order)


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  • Access to different types of high quality biological materials from patients will speed up development of cancer diagnosis and treatment

  • The more we understand the disease, the better we can target treatment – but the scientific work will take time and money


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  • We gratefully acknowledge the financial support for the project from WORD, and also the support from the pathologists, cancer MDTs, and BMS in Wales

  • A big thank you to our most important supporters – the patients of Wales


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