Extending our understanding of the molecular events in cancer growth and progression requires detailed correlations of molecular characteristics with biologic tumor behavior and host response. These data are essential to the design of new, more effective therapies, better application of conventional treatments and prevention strategies for tumor relapse. An essential prerequisite is availability of complete clinical, demographic, and treatment data that are integrated with molecular data from well-characterized human tumor and serum samples as well as our unique panel of head and neck cancer cell lines that serve as in vitro and in vivo model systems for investigation of novel agents or mechanisms. To support the research efforts of investigators in this UM-HN SPORE program, the NCI and other SPORE programs, a comprehensive tissue procurement, processing, storage, head and neck cancer cell line bank, distribution process and data management system is proposed.
This core represents collaborative efforts of basic scientists, anatomic pathologists, clinicians and data managers. It builds our prior experience in collecting, storing and distributing tissues among our Head and Neck Oncology Program Investigators and the experience of our UM Cancer Center Tissue and Tumor procurement Core, as well as cooperation with the UM Prostate SPORE. Detailed distribution rules and standardized processing for whole blood, serum, fresh tissue with proper imbedding and frozen storage, tissue in RNA Later, paraffin embedded tissue, immunohistology, tissue microarray, and cell culture preparation are included. A detailed descriptive relational database including tumor characteristics, patient demographics, health behaviors, co-morbidities, family history, treatment and follow-up data is linked with the tumor repository data and each investigator's laboratory by a secure Head and Neck web-based database called BioDBx that is interfaced with the clinical UM Health System data repository (Care Web). Flexibility is provided to meet specific needs of any project and incorporation of new technologies for future projects or collaborations with outside investigators. We have proposed a model system that will be a resource that maximizes superb tissue-clinical data availability for studying these relatively uncommon head and neck cancers by the entire NCI SPORE community.
The Tissue Core has four tissue microarrays constructed and available for study including TMA 38, 56, 72 and the recently completed TMA 70. Two additional TMAs are close to completion. The Tissue Core is also working on construction of a TMA of squamous cell carcinomas that are not linked to a specific clinical trial, for investigators who are studying the basic biology of this tumor rather than treatment response. Immunostaining and analysis of TMA 70 has begun with antibodies for p53, Bcl2 and Bcl-xL. Slides are evaluated and the results are recorded using the tissue profiler computer system.
Specimen collection. During the period 07/01/2008 -03/31/2009 (9 months) the Tissue Core collected 694 new specimens from 163 patients. These specimens included 5 normal tissue samples from 5 patients, 21 tumor samples in RNALater from 21 patients, 110 saliva samples from 105 patients, 248 serum samples from 163 patients, 65 tumor specimens from 51 patients and 245 whole blood specimens from 162 patients. During this period a total of 206 new subjects were consented as SPORE patients, thus the proportion providing specimens equals nearly 80 % of enrolled patients. The total number of specimens processed, bar-coded, aliquoted, and stored equaled 694 for the 12 month period.
Tissue micro arrays: The Tissue Core has prepared 5 new tissue micro arrays related to completed clinical trials in the past year: TMA 99 representing the surgical salvage specimens from UMCC 9520; TMA 116 representing the post chemotherapy and post chemo/RT surgical salvage specimens from UMCC 9921 oral cavity and oropharynx cancer trial; TMA117 representing both pre-treatment and salvage specimens from UMCC01-056 larynx cancer trial treated with chemo alone; and TMA 123 representing pretreatment biopsies from the UMCC0221 oropharynx trial.
Patient sample distribution. In the period covered by this report there were 12 requests for patient tissue core materials. The majority of these 8, were for Tissue Microarray slides, two were for paraffin slides of tumor tissue, one for whole blood samples and 1 for serum specimens.
Histopathologic Review and related tasks. For the construction of each of the TMAs retrieval of pre-treatment biopsy tissue blocks, cutting of new sections, and histopathology review was required. Subsequently, Tissue core processing of each block, with barcoding was carried out, then TMAs were constructed by the Cancer Center TMA core. Cores were were taken from tumor and normal areas of the blocks and DNA samples were prepared and stored as "child' samples. For each TMA request and staining procedure histopathology scoring was required and the data was then compared to the map and entered into BioDbx for analysis and comparison to patient outcome.
Cell line characterization, banking, and distribution. The UM-SCC head and neck and other cancer cell line collection is one of the best characterized collections in the world. We have recently completed genotyping of more than 90 cell lines including 73 UM-SCC lines described in a recently accepted manuscript that is being modified per the reviewer's suggestions. In addition all of the HNSCC cell lines have been tested for HPV and the UM-SCC-47 line which contains `18 copies of integrated HPV16 is highly requested by investigators around the world. The complete table of cell lines is also being added to the SPORE web site for easy access by other SPORE investigators. In the period from July 1, 2008-March 31, 2009 132 cell line samples have been distributed. Of these, 54 were to internal U of M SPORE investigators, 26 were to Non-U of M SPORE investigators, 14 were to External SPORE collaborators and 38 were to other external investigators.