2008 Summer Meeting - Leeds - The Pathological Society of Great ...

S9Incipient testicular germ cell neoplasia: biology and possibleclinical interventionL Looijenga 11 Erasmus MC, RotterdamWithin the human testis, various germ cell lineage-derived cancers can befound. In neonates and infants, teratomas and yolk sac tumours are diagnosed,i.e., type I Germ Cell Tumours (GCTs), for which no precursor cells areidentified so far. The adult testes predominanly develop type II GCTs, i.e.,seminomas and nonseminomas. The III GCTs of elderly are rare and benign, ofwhich the precursor cell is likely a primary spermatocyte.Type II GCTs originate from carcinoma in situ (CIS). CIS and seminoma cellsmimic primordial germ cells/gonocytes, a maturation stage normally absent inadult testis. The embryonic stage is demonstrated by expression of OCT3/4.OCT3/4 is proven to be a highly informative diagnostic marker for CIS,seminoma and embryonal carcinoma. In addition, it can be used as target for anon-invasive screen, in which the diagnosis is based on semen investigation.Most recently, SOX2 is identified as a diagnostic marker for embryonalcarrcinoma and SOX17 for seminoma (and CIS). This provides an informativediagnostic profile based on three genes.Besides undescended testis, infertility (combined with microlithiasis) andfamilial predisposition, disorders of sex development (DSD) is a risk factor fortype II GCTs. Specifically, hypovirilization and various forms of gonadaldysgenesis, in the presence of the so-called GBY region, result in an increasedrisk. In case of gonadal dysgenesis, gonadoblastoma can also be the precursorlesion. Knowledge about the pathobiology allows development of methods forearly diagnosis in males with an increased risk.S11Organ RegenerationJ Southgate 11 University of YorkA shortage of donor organs, the ageing population and growing quality-of-lifeexpectations are all driving research to find novel solutions for organregeneration. Tissue-engineering is a multidisciplinary approach thatincorporates cell biology, materials sciences and engineering into theconstruction of tissues suitable for transplantation. Although the objectives areclear, there are still a number of major scientific and technical obstacles toprogress, including how to manipulate in vitro-expanded cells to formorganised, functional tissues. The urinary bladder will be used as an example toindicate the range of strategies being pursued and to discuss progress andunresolved issues in the field.S10Stem CellsRPoulsom 11 Cancer Research UK - London Research InstituteStem cells have been claimed to offer the basis for cell-based therapies for awide range of diseases, although significant problems exist. Therapeutictransfer of haematopoietic stem cells is now well established and effective, butattaining this has required considerable experimentation in animal models andin patients over several decades. Our understanding of other adult stem cellpopulations is nowhere near so complete. There is good evidence for theirexistence in gut and skin, yet there is debate over their existence in the liver andkidney, and over the value and reproducibility of putative stem cell markerssuch as CD133 and lgr5 (GPR49). Therapies relying on cells that exhibit certainstem cell characteristics (such as clonigenicity and the ability to generatedifferentiated daughter cells) are being developed, with some notable progressin regeneration of corneal epithelium (from cultured limbal stem cells) and ofthe skin (from cultured and genetically engineered epidermal stem cells).Retrovirus-induced overexpression of key stem cell proteins induces apluripotent stem (iPS) cell phenotype in cultured human and mouse fibroblasts.iPS cells have the potential to replace embryonic stem (ES) cell cultures for theisolation of tissue-specific stem cells for regenerative medicine. There aresignificant inherent risks from multiple retroviral integrations, yet iPS cellshave already been used to generate haematopoietic stem cells capable ofrescuing mice that model human sickle cell disease. Better understanding ofstem cells? behaviour, normally and during tissue regeneration, may helpdevelop safer future therapies.S12Spinal degenerative diseaseT Freemont 11 Head of Research School in Clinical and Laboratory Sciences, Universityof ManchesterIt is now recognised that back pain is caused by degeneration of theintervertebral disc. The analysis of degeneration by molecular pathology hasshown that this is an active disorder and very different from that implied by theterm “degeneration”. Work from our laboratory has shown that the processes ofdegeneration are triggered by a change in the normal cytokine biology of thedisc, to one that favours catabolic rather than anabolic processes. All theavailable data indicate that the key cytokine is IL-1 and the degenerationmechanism is driven by MMPs, and related degradative enzymes.The resulting back pain is caused by loss of disc height and nerve ingrowth.Demonstarating that these mechanisms are key to degeneration, has alsoallowed the identification of molecular and other targets, to reverse theprocesses of degeneration. Amongst these are the use of stem cells, novelbiomaterials and delivery of regulatory biologics to regenerate normal disctissue in the site of previous degeneration.90 Summer Meeting (194 th ) 1–4 July 2008 Scientific Programme