The European Society of Toxicologic Pathology (ESTP) offers every second year an award for a thesis in toxicological pathology, sponsored by Boehringer Ingelheim Pharma GmbH & Co. KG.

Winners in 2006:

1. Dr. Heike Marxfeld
   honored with EUR 5,000
   Dr. Heike Marxfeld is awarded for her PhD-thesis entitled "Gene expression profiling of spontaneous and induced mammary tumors of the rat." The topic of this thesis is of high relevance for toxicologic pathology, as mammary tumors are among the most frequent spontaneous tumors in rats and are known to be induced by a wide variety of chemicals.
   
   The concise literature review introduces in an adequate manner into the topic of mammary tumors in humans and rats, their classification, and the role of chemical induction. All experiments were faithfully designed and conducted. The sophisticated methodology is state of the art and centers around gene chip analysis and confirmatory immunohistochemistry and RT-QPCR for selected genes. Two main results were that (1) fibroadenomas have a gene expression profile distinctly different from adenocarcinomas and (2) several genes were identified that could discriminate between spontaneous and DMBA-induced adenocarcinomas. All results were thoroughly discussed and interpreted resulting in two major conclusions, that (1) fibroadenomas in rats may not be a precancerous lesion and (2) gene expression profiling may be a useful tool in differentiating between spontaneous and induced mammary tumors in rats.
   
   With her PhD-thesis Dr. Marxfeld demonstrates in an exemplary manner the potential that evolves from the combination of genomics technologies with established methodologies of toxicologic pathology. Her results are of high value as they improve the validity of the rat as an animal model for carcinogenicity testing.
   
   Reference:
   Marxfeld H. Gene expression profiling of spontaneous and induced mammary tumours of the rat. [PhD-thesis] Hannover (Germany), School of Veterinary Medicine, Hannover, 2005
   
   
2. Dr. Stephanie Deppenmeier
   honored with EUR 3,000
   Dr. Stephanie Deppenmeier is awarded for her PhD-thesis entitled "Pathomorphologic phenotyping and expression pattern analysis of hCD59-transgenic pigs designed for xenotransplantation." This thesis addresses a topic of high relevance for public health: The generation of human xentotransplants in an animal model to overcome the shortage of human donor organs. This was attempted by generation of pigs transgenic for the human complement regulator hCD59 which should inhibit the activation of the human complement cascade responsible for acute transplant rejection.
   
   The literature review comprehensively introduces into transplant rejection mechanisms, the role of CD59 in various species, and the characterization of CD59 expression in transgenic pigs. The methods chosen for characterizing the transgenic pigs are adequate to fully describe their phenotype. By the application of PCR, Dr. Deppenmeier demonstrated that hCD59 DNA was present in all organs and tissues examined, indicating successful incorporation of the gene construct. The detection of m-RNA by Reverse Transcriptase-PCR revealed that the gene was widely expressed, but not in all organs and with inter-individual differences. Immunohistochemical protein detection added that in certain organs the protein expression showed a patchy distribution pattern. These results were completed by histopathology and virology to characterize the health status of the animals. The results were comprehensively discussed leading to the conclusion that the application of transgenic pigs for generation of human xenotransplants is problematic since the hCD59 protein expression showed an uneven distribution pattern.
   
   This PhD-thesis demonstrates in an exemplary manner the potential of new methods in pathology when applied on a high level of scientific judgment.
   
   Reference:
   Deppenmeier S. Pathomorphologic phenotyping and expression pattern analysis of hCD59-transgenic pigs designed for xenotransplantation [PhD-thesis] Hannover (Germany), School of Veterinary Medicine, Hannover, 2005
   
   
3. Dr. Guillaume Cornelis Maria (Guy) Grinwis
   honored with EUR 2,000
   Dr. Grinwis is honored for his thesis entitled "Health effects of some major aquatic pollutants in European Flounder: Laboratory experiments with emphasis on histopathological and immunological aspects." This doctoral thesis addresses in an exemplary manner one major aspect of environmental safety, the accumulation of chemicals in marine sediments and its health effects on fish populations. He has chosen a highly relevant test model, the European founder, based on the high prevalence of liver tumors, skin ulcers and viral lymphocystis disease in this species.
   
   All experiments were adequately and accurately designed and conducted. The selection of test chemicals, an organotin compound (TBTO), TCDD, and a PCB, is adequate and representative. By application of histological, morphometrical, immunohistochemical, immunological and scanning electron microscopical techniques it was clearly demonstrated, that concentrations of TBTO in the order of high field values caused effects on the lymphoid system indicative of immunosuppression. Short-term effects were confirmed in even more relevant long-term experiments. All results were comprehensively discussed, including the possible effects of exposure to mixtures of chemicals under field conditions.
   
   This thesis shows impressively that toxicologic pathology plays an important role in environmental safety assessment. It is pioneering in the pathology of the European flounder.
   
   Reference:
   Grinwis G. Health effects of some major aquatic pollutants in European Flounder: Laboratory experiments with emphasis on histopathological and immunological aspects [Doctoral thesis], University Utrecht, The Netherlands, 2006
   
   

La Grande Motte, France, September 28, 2006