PREFACE

The investigations on which this thesis is based were initiated in May 1991, and were carried out at the Stereological Research Laboratory during my 4-year employment as research associate. However, in fact it all began in 1985 with the invention by Hans Jarrgen G. Gundersen and EvaY B. Jensen of a new stereologic estimator of mean particle size, which could be applied to ordinary tissue sections. This estimator was first tested for the purpose of objective malignancy grading by Karsten Nielsen and co-workers in 1986, and proved successful in bladder cancer. Karsten Nielsen defended his thesis on the subject in 1991. He was soon followed by Flemming Brandt Sarensen, who applied stereology to a great number of tumor types, defending his thesis in 1993. Still, it was clear that a lot had to be done to further refine and verif) the technique. At that stage, I was introduced to the field, which very soon attached my interest. Clearly, this work had not been possible without the patient guidance, enthusiasm and generosity of my scientific supervisors, Hans Jargen G. Gundersen and Flemming Brandt Sarensen. The skilful technical assistance of Anette Funder, Lise L. Gjerrild, Hanne Kaas, Anette Larsen, MajBritt Lundorff, Tina Nygaard and Marianne Rasmussen is greatly appreciated. Indeed, I thank the entire Laboratory staff and its associates, among others, Thomas F. Bendtsen, Roger Bjugn, Ryoji Chiba, Henrik Clausen, Karl-Anton Dorph-Petersen, Ricardo E. Feinstein, EvaY B. Jensen, Jens Peter Krogstrup, Jytte 0. Larsen, Anemette Lakkegaard, Karsten Nielsen, Jens R. Nyengaard, Bente Pakkenberg, Trine Tandrup,Yong Tang and Mark J. West, for many good moments in a warm and inspiring atmosphere. I also thank co-authors for their valuable contributions, especially Vibeke Jensen, Bernt Nielsen and Hans Svanholm. Professor Jan P. A. Baak is acknowledged in particular for inspiring companionship and for his approval of the inclusion in the work of some at this time unpublished results. The departments of pathology at Randers Centralsygehus, Aarhus Amtssygehus and Aarhus Kommunehospital, and the department of oncology, Aarhus Kommunehospital, are acknowledged for providing the necessary material as well as good conditions for my research. Moreover, I thank the Danish Breast Cancer Cooperative Group (DBCG) for providing high quality follow-up data. Last but not least, I am indebted to my beloved wife, Ulla, for standing by my side, taking care of everything else, and to our two magnificent boys, Niels and Jesper, for being so. Although the work, at times, may be somewhat technical, one should bear in mind that behind each drop-out in survival functions is a personal tragedy. Dedicating my work to the memory of these people, it is my sincere hope that I might bring the understanding of the dreadful disease of cancer just a little bit further. This is, after all, what its all about. This work was primarily supported by several grants from the Danish Cancer Society. Grants were provided also by Valdemar and Thyra Foersoms Foundation, the Danish Foundation for the Advancement of Medical Science, King Christian Xs Foundation, Astrid Thaysens Foundation, DesirCe and Niels Ydes Foundation and Novos Foundation. Individual, original papers were additionally supported by grants from Kathrine and Vigo Skovgaards Foundation, the Hajmosegaard Foundation, Else and Mogens Wedell-Wedellsborgs Foundation, Ib Henriksens Foundation, Jacob and Olga Madsens Foundation, Lily B. Lunds Foundation, August Frederik Wedell Erichsens Foundation, Novo Nordisk Foundation, M. C. and J. K. Moltums Foundation, Aage Bangs Foundation, and Frits, Georg and Marie Cecilie Gluds Foundation. hhus , April 1998 Morten Ladekarl