Michael Höckel MD, PhD is Professor emeritus of Gynaecology at the University of Leipzig and Distinguished Affiliated Professor of the Technical University of Munich, Germany.

He is also Director of the Leipzig School of Radical Pelvic Surgery.

Based on extensive spatiotemporal pattern analysis of developing human tissues and malignant tumours he proposes a new tumour model considering cancer as inverse morphogenesis. He demonstrated with more than 1000 patients suffering from cancer of the lower female genital tract that redefining tumour staging and surgical treatment according to this concept significantly improves the clinical results. Ontogenetic staging proved to be superior to all previous staging systems in predicting overall prognosis. 5 year survival rate after cancer field resection without adjuvant radiation exceeded survival after conventional radical surgery with adjuvant radiation by up to 20%.


THE ORDER OF CANCER: MALIGNANT TUMORS PROGRESS BY INVERSE MORPHOGENESIS

Michael Höckel

Leipzig School of Radical Pelvic Surgery

Leipzig, Germany

 

Most cancer researchers accept a tumor model that is based on the principle of random variation and selection. Likewise, clinical oncologists consider the propagation of invasive cancer cells a stochastic process. However, a variety of experimental and clinical facts are not consistent with these tenets.

We propose a theory of cancer that involves a principle of order established through the self-organizing process of morphogenesis. Whereas clinical cancer initiation is caused by somatic mutations, malignant progression is considered to result from attractor-driven “inverse morphogenesis”, an epigenetic process eventually modulated by but not dependent on additional mutations.

The theory is based on the following assumptions: Immature metazoic cells are self-organizing complex systems assembling collectives (tissues), functional multipopulation units (organs) and, finally, organisms. All stable states of these systems at the hierarchical levels from the living cell to the living organism represent attractors in the corresponding state spaces established by evolution and maintained by the cell’s genetic regulatory network. Instrumental for this complex regulatory system is both, the genome and its three-dimensional organization by hierarchical folding. Morphogenesis is considered as a process determined by “forward” genomic folding increasing topobiological information processing along with the dominance of higher-level attractors such as tissue, organ and organism attractors. Cancer progression  is proposed to involve the reverse process of “backward” genomic unfolding decreasing topobiological complexity at increasing plasticity with the dominance of the cancer cell attractors over the higher-level attractors. Both forward and backward transitions in chromatin organization are induced by proliferation-driven attractor destabilization.

The order provided by the sequence of attractor transitions and the defined topography of the permissive territories can be exploited for more accurate tumor staging and for locoregional tumor treatment with higher curative potential.

The lecture will illustrate the complex theory with the examples of carcinomas of the uterine cervix and vulva. The development of the female genital tract from Carnegie stage 11 to adulthood will be outlined and displayed with ontogenetic anatomical maps. Ontogenetic anatomy is applied for local and regional tumor staging and for the treatment with cancer field surgery such as total mesometrial resection and vulvar field resection combined with therapeutic lymph node dissection. The favorable clinical results of these treatments obtained with a large cohort of patients with long-term follow up are presented as proof of principle.