As for the formation of new lymph vessels, this isn't in response to a need to receive the means to survive, but to spread from a distance. “And yet, when we analyse lymph nodes present in operative specimens after surgery on digestive endometriosis, endometrium can be found there ⁽³⁾; we can therefore establish a parallel with the spread of a cancerous tumour”, Michelle Nisolle says.

A question that logically comes to mind: is the risk of cancer increased in women with endometriosis? Yes and no. “In fact, the actual endometriosis rarely becomes cancerous, but if the lesion is left to evolve after the age of 50, there is nevertheless a small risk. That’s why we recommend surgical resection. On the other hand, it has been shown that these women have a statistically higher risk of developing Hodgkin’s disease and melanoma. Caution should be exercised”.

A bothersome fibrosis

But the area in which Michelle Nisolle has probably carried out the most research is the fibrosis secondary to the endometrial foci, in particular in the rectal wall. “Fibrosis is a natural evolution of the inflammatory endometriotic lesions; in fact, sometimes there is a spontaneous recovery (in the best cases) but most often, this fibrosis corresponds to a reaction of the host tissue infiltrated by the endometrial cells.  The fibrosis infiltrates the rectal wall and causes the tissue to shrink, thus reducing the internal diameter of the organ. It is a little known yet very important phenomenon”, she stresses, “because it explains why some patients are in such pain. Officially, this only concerns 5% of cases of endometriosis, but this figure refers to established cases of rectal endometriosis; this doesn’t take into account endometriosis of the pelvic cavity which infiltrates towards the vagina and the rectum. So in reality, the problem is much more widespread.” Very often, it is treated by a resection of this terminal part of the intestine, an operation that isn’t entirely risk-free (anastomosis linkage, faecal peritonitis …). “I’m fighting for women to be offered less destructive treatment. First of all, by making the diagnosis more quickly to avoid overly complex situations, and then by developing a more conservative operating technique, by endeavouring to ‘shave’ the rectum rather than systematically removing it. We’re working to achieve that in collaboration with digestive surgeons.”

Finding a surgical approach that is more respectful of the anatomy is one thing, understanding the why of fibrosis is another. Always wanting to link the clinical with research, Michelle Nisolle has also explored this phenomenon in the laboratory. “Again with our experimental mouse model, we studied the transplantation of endometrial lesions in two types of mice, completely immunodeficient (SCID mice) on the one hand and only partly immunodeficient (nude mice) on the other. We observed that the endometrium transplanted under the skin causes a serious fibrous reaction in nude mice but not in the other ones, where the lesion maintains its morphological characteristics typical of the endometrium. In other words, in the completely immunodeficient mouse, the endometrium continues to develop normally, whereas in animals with partial immune response, we obtain a model of endometriosis as observed in our patients.” In clinical terms, this means that when endometriosis is accompanied by pronounced fibrosis, it is because the ectopic endometrium generates a greater immune reaction around it in the host tissue. Knowing that it is the inflammatory reaction that creates the fibrosis  could have an impact on a therapeutic level. Identifying the molecular actors responsible for this fibrosis would allow us to develop new strategies to inhibit this interaction between the endometrial cells and the host tissue.

(3) Brichant G, Blacher S, Alvarez ML, Munaut C, Foidart JM, Nisolle M. Computer-assisted quantification of angiogenesis in deep infiltrating endometriosis. 2012 (submitted to Human Reproduction).