In recent years, the need for controlling the 'secondary use' of
human biospecimens for research purposes at the NKI became more
apparent. To ensure human material is used properly and
efficiently, especially in the case of scarce, valuable samples, a
facility for use of NKI biobank materials was desired. Therefore,
in 2011, the Core Facility Molecular Pathology & Biobanking
(CFMPB) was founded.
The CFMPB facilitates the use of NKI biobank materials for
translational research. For all research projects, in which the use
of NKI biobank materials is proposed, the Core Facility has to be
contacted by the researcher. The CFMPB confirms that the
Translational Research Board approves the usage of the material,
does the sample handling (logistics), generates derivative
biospecimen samples, and stores scientific results. Currently the
facility's resources consist of a team of dedicated (lab) staff,
dedicated lab space and equipment, and an in-house developed
application and request tool.
Application and Request Tool
In collaboration with the IT department we are developing a web
application named the Application and Request Tool (ART) in a lean
and agile way. ART serves many users; Researchers can access ART
for online application of studies and biospecimen-and lab-work
order requests. Pathologist, clinicians and basic scientists use
the system for reviewing and approving the study applications. The
CFMPB staff uses ART as a workflow system, handling the
applications and requests. All this user activity is stored in the
ART database and by doing so, information about the applications,
biospecimen identifiers, succeeding actions and derivatives
accumulates. This results in a rich data source allowing the CFMPB
to further optimize and stimulate proper use of NKI-AVL biobank
specimens. 'ART' includes a (connector based) search tool option to
query existing hospital data systems as PALGA, LMS, Biometrics
tumor registry, GLIMMS, etc.
ART is developed in .Net (C# and asp.net), stores the data in a
Microsoft SQL Server database, is supported and hosted by the IT
department and is only accessible on the intranet (http://cf-mpb.nki.nl).
Study Application and Approval
The CFMPB follows a standard procedure for all requests of human
biospecimens for (translational) research. The NKI Translational
Research Board (TRB) has decided that each study using NKI Biobank
material (secondary use of diagnostic material) needs to be
reviewed by three internal NKI reviewers.
1. a relevant pathologist (tissue) or clinical chemist
2. a relevant clinician
3. a relevant basic scientist
The CFMPB, on behalf of the TRB, will verify the suitability of
the reviewers for the particular application. The TRB approval
procedure for 'secondary use' of human material (according to Dutch
legislation (Code of conduct)) is, following positive
recommendation of the Medical Ethical Committee (NKI), approved by
the Board of Directors NKI.
Only NKI employees can submit applications. External applicants
need to initiate a collaboration with an NKI employee. The NKI-AVL
partner will be responsible for the use of the material and should
be involved in the research and publications. In many cases, a
Material Transfer Agreement (MTA) from the Technology Transfer
Office is required (see website of the NKI TTO).
NKI Biobanks regulations and Legislation
The NKI has several Biobank collections and these biospecimens
can only be requested for research purposes through the CFMPB. Most
of these samples are collected during diagnostic procedures or
treatment and are stored primarily for patient care. They can be
used for research purpose, 'secondary use', according to the Dutch
legislation: Code of Conduct (FEDERA) and WGBO (Wet op de
geneeskundige behandelingsovereenkomst). The Code of conduct is the
Dutch standard for collection, storage and use of human materials
for scientific research. http://www.federa.org/gedragscodes-codes-conduct-en
Part of the material is specifically collected for (predefined)
scientific research and stored primarily for research. In these
cases there is always explicit informed consent. Use of this
material is regulated by WMO (wet medisch wetenschappelijk
onderzoek met mensen/law for medical scientific research with
interventions in humans), WGBO and Code of Conduct Federa.
These 'de novo' studies always need approval by the Medical Ethical
Department of Pathology (secondary use and de novo)
1. Biobanks of tissue collected during the diagnostic and
treatment process of patients
2. Paraffin tissue archive (> 1970)
3. Glass slides archive (> 1970)
4. Frozen tissue biobank (> 1985)
Department Clinical Chemistry (de novo and secondary use)
1. 1.Serum collection (>1982)
2. Blood biobank (>2010)
CFMPB (secondary use)
4. Digital slides
5. IHC data & results
The CFMPB has a fully equipped and dedicated
histology/immunohistochemistry (IHC) lab. Nearly all IHC is
performed using the BenchMark Ultra (Ventana, Roche) automated
stainer, in close collaboration with the diagnostic pathology
All routine IHC diagnostic protocols are also implemented at the
CFMPB and can be requested for research studies. Ample
experience is available for the development of new antibody
staining protocols. Elaboration and optimizing of staining
protocols is performed in close collaboration with the requesting
scientist and involved pathologist.
We are in the process of implementing digital pathology for
scoring and storage of all research IHC using Aperio ScanScope
(Leica), Spectrum and Slidepath software tools in combination with
To guarantee standard quality all DNA and RNA isolations from
NKI Biobank material (FFPE, FF, serum, and blood) are performed by,
or under supervision of, the CFMPB technicians. All samples will be
handled and stored in the dedicated CF lab (pre-PCR, QC conditions)
under supervision of the coordinating technicians according to
standard protocols modified and adapted to the specific
requirements per project. Small (pilot) studies (less then ~10
samples) will be carried out by the CFMPB technicians. All larger
studies require technical support from the applicant.
We register all used samples and results obtained (IHC, DNA/ RNA
quality and quantity). All resulting samples will be coded with a
unique (bar-coded) core-study number before distribution for
further use. The decoding key will be kept in a secured database of
the pathology department (and will be, depending on the study
design and consent, always accessible for the applicant).
The central contact of the CFMPB is CFMP@nki.nl or +31 20 512
We are located at the department of Molecular Pathology.
We are collaborating in the following projects:
- FP7-HEALTH-2010-2.4.1-2 EUROCAN " A European Platform for
Translational Cancer Research " contribution in WP10
Biobanking/WP11 Clinial Epidemiology C
- CTMM TraIT "Translational IT". Involved in WP3
Biobanking, WP7 digital pathology and WP5 FP7
- HEALTH-2007-2.4.1-11 COGS "Collaborative Oncological
Gene-environment Study" -BCAC (with MK Schmidt) P7
- BASIS "Breast Cancer Somatic Genetics Study"
(Subcontractor with Laura Van't Veer)
- An alpha-E-catenin (CTNNA1) mutation in hereditary diffuse
Majewski IJ, Kluijt I, Cats A, Scerri TS, de Jong D, Kluin RJ,
Hansford S, Hogervorst FB, Bosma AJ, Hofland I, Winter M, Huntsman
D, Jonkers J, Bahlo M, Bernards R.
J Pathol. 2012 Dec 3. doi: 10.1002/path.4152.
- Indentification of recurrent FGFR3 fusion genes in lung cancer
through kinome-centred RNA sequencing.
Majewski IJ, Mittempergher L, Davidson NM, Bosma A, Willems SM,
Horlings HM, de Rink I, Greger L, Hooijer GK, Peters D, Nederlof
PM, Hofland I, de Jong J, Wesseling J, Kluin RJ, Brugman W,
Kerkhoven R, Nieboer F, Roepman P, Broeks A, Muley TR, Jassem J,
Niklinski J, van Zandwijk N, Brazma A, Oshlack A, van den Heuvel M,
J Pathol. 2013 Jul;230(3):270-6. doi: 10.1002/path.4209.