Scientific Concept of the National Cohort (status ... - Nationale Kohorte

A.3
A.3 Study design
routinely prepared for diagnostic evaluation. Prepared in this way, tissue samples remain
stable for a long time (in principle for periods up to 100 years) and can be used further for
histological and molecular analyses. These formalin-fixed, paraffin-embedded tumor tissues
represent the basis for preparing histological slides.
Generally, tumor materials are not used up by the diagnostic process and remain in storage
for several years at the respective pathology institutes, until they are discarded because
of space limitations and financial restrictions. Thus, most diagnostic archives are relatively
short-term and, in addition, they do not generally have common standards and rules for access
to materials. For future research based on the tumor tissues within the National Cohort
it is, therefore, essential to establish a central tumor tissue bank that provides quality-assured
storage, documentation, assessment, and release of these materials for research purposes.
The general collection of fresh-frozen tumor samples by the National Cohort is neither feasible
nor is it necessary for the majority of research questions. Owing to various recent
technical innovations, the vast majority of relevant molecular analyses can be performed
with formalin-fixed, paraffin-embedded tumor tissues. Largely unrestricted analyses will be
possible in the areas of DNA analysis (genomic imbalances, translocations, mutations), epigenetics
(methylation assays), transcript (RNA expression) analysis, and analysis of noncoding
RNAs, and histology (including special stains and immunohistology).
From formalin-fixed, paraffin-embedded tumor tissues, standardized derivatives such as
nucleic acids, protein extracts, and multitissue arrays can be produced for further analyses
in the context of well-planned, nested projects, making efficient use of the limited tumor
materials available. For reasons of efficiency, quality control, and subsequent archiving and
distribution, these derivatives will be produced in the context of the central tumor tissue
bank. Furthermore, the use of tissue materials for various laboratory analyses generally
requires that the material be re-examined by pathology experts, and this, too, should be
performed at an institution that can provide the relevant histopathological expertise.
Suggested site for the tumor biobank (NCT, Heidelberg)
The existing infrastructures of the tissue biobank of NCT in Heidelberg will provide optimal
support for the tissue biobank of the National Cohort for the following reasons:
� Ethical and legal situation: The tissue biobank of NCT in Heidelberg has received
broad ethical approval for prospective tissue collection and retrospective use of previously
collected samples for research purposes.
� Project management and experience: With more than 620 completed projects, the
NCT tissue biobank has the highest project experience in centralized tumor banking
in central Europe. Active project management in standardized project tracking and
specific experience in supporting large population-based epidemiologic studies are
available.
� Technical standards: The tissue biobank of NCT in Heidelberg offers a broad technology
platform (all relevant histological methods, multitissue array production, nucleic
acid technology, microdissection, virtual microscopy, and image analysis). Especially
tissue microarray technology joined with virtual microscopy is of great use for managing
decentralized tissue-based projects and was implemented successfully in the past.
� Quality management: The tissue biobank at NCT has implemented a comprehensive
quality management system and is the only accredited tissue biobank in central Europe.
All processes are guided by SOPs and are monitored by internal and external
audits. The tissue biobank is supervised twice annually by its advisory board, annually
by NCT, and every 3 years by an international review board.
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