Pathology research covers a wide spectrum from basic biomedical research to applied clinical research. The field is expanding rapidly as a result of advances in molecular biology. The department emphasises translational research of basic scientific findings into clinical application and the effective investigation of clinical problems in the laboratory. While we work with all major disease categories, the main focus of our applied clinical research is cancer. Our research identifies biomarkers to improve diagnosis by e.g. distinguishing between cancer cells and other cell types, predict the development of diseases (for example in cancer prognosis), and optimise treatment by e.g. identifying patients who will benefit from targeted cancer therapy. The presence of biomarkers in tissue is demonstrated by combining traditional microscopy with advanced molecular methods, a combination that has given rise to a new area of expertise: molecular morphology. At the same time, we use novel scanning and digital-imaging techniques to increase the precision of marker identification and measurement, and to automate processes.
We have a unique source for research in the form of a very large clinical biobank that already consists of millions of tissue samples from patients and dates back to the founding of the department in 1959. Tissue is taken from all samples sent for diagnostic examination at the pathology department. The tissue is filed for ever and registered in the laboratory system Patobank that covers the whole country. Thus, it is possible to search for and localize e.g. 100 patients with a rare cancer disease quite easily. The tissue samples are filed fixed in formalin and embedded in paraffin.
Employees from different professions in the department do research and cover a wide range of topics within the clinical and more basic research. A common thread in our joint research strategy is to combine expertise in the microscopic morphology with the molecular methods. This combination gives a unique knowledge of disease changes, and, in particular, this is used to characterize the microenvironment and the tumour microenvironment in the sick tissue being researched in. The close interaction between tumour cells, stroma cells, immunocells and inflammatory cells in the tumour microenvironment is important for the development of malignant diseases and is the main topic for our research.
To implement the common research strategy the department has developed a number of methods to take advantage of the valuable clinical biobank and to extract as much data as possible.
Immunohistochemistry is used to show protein where antibodies show specific antigens. Normally, 1-2 antigens are shown in a section, but the goal is to be able to show up to 6 markers and even in the same cell. This method is called multiplex immunofluorescens where the immunofluorescens-stained slides are combined with ordinary HE-stained slides thereby visualizing the morphology of the tissue at the same time. This is only possible using advanced picture analyzing systems where the stained slides are digitalized and virtually laid on top of each other. The department's researchers have also participated in developing advanced techniques to clear proteins on a large scale from formalin fixed tissue for proteomics.
In the future slides will be digitally scanned and examined on an electronic screen. Digitalization of the slides opens up possibilities for additional analyses based on machine learning/artificial intelligence.
The staff of the department has many years of experience in using molecular methods for analyzing for nucleic acid in tissue. Partly in situ methods on tissue samples partly based on experience in working with partly broken-down/disintegrated DNA and RNA cleared from tissue, where lately modern sequencing methods are used and optimized. These state-of-the-art molecular methods combined with our expertise in microscopic morphology have large advantages together with the access to our unique tissue biobank.
We use these state-of-the-art methods for research projects in collaboration with regional, national and international collaborators. E.g. collaboration with the Department of Molecular Medicine about cancer in the bladder, prostate and colon, collaboration with the Department of Biomedicine about malignant melanoma, collaboration with the Department of Clinical Epidemiology about cancer in the breast and intestines, collaboration with the Department of Oncology about breast cancer and collaboration with the Department of Haematology about lymphoma.
To combine knowledge about the architecture of the tissue and protein expression with molecular biological methods such as DNA and RNA sequencing is valuable in the strategy to characterize tumour microenvironments. The spatial connection between tumour cells and the inflammatory cells in the tumour microenvironment is important to be able to address a biological problem.