Among several forms of pancreatic cancer, one of them affects specifically women, often young. How is this possible, even though the pancreas is an organ with little exposure to sex hormones? This pancreatic cancer, known as "mucinous cyst," has strange similarities with another mucinous cancer, affecting the ovaries. By conducting large-scale analyses of genomic data, researchers at the University of Geneva (UNIGE) and at the University Hospitals of Geneva (HUG), Switzerland, in collaboration with colleagues from the United States have provided an answer: both tumours originate from embryonic germ cells. While still undifferentiated, these cells migrate to the reproductive organs. On their way, some can mistakenly stop in other organs, bringing a risk of tumour that may occur 30 years later. By allowing a better classification of these mucinous tumours, this study, to be read in the Journal of Pathology, paves the way for a more appropriate and personalized management aligned with the tumour's origin.
Mucinous tumours of the ovary and pancreas affect young women -- between 30 and 40 years of age. They take the form of a large cyst, a kind of ball filled with liquid. Rare they account for about 3% of ovarian and pancreatic cancers they are usually treated by surgery. Taken in time, the cancerous cyst is completely removed. However, in 15% of cases, the cyst breaks before surgery; the cancer cells spread into the peritoneum, giving rise to metastases that are highly resistant to chemotherapy. In such cases, the survival prognosis of patients does not exceed one year.
A common origin
Why is a non-gynaecological cancer almost exclusively female? What is the link between the ovary and the pancreas? "It is only during embryogenesis that these organs are really close. At the very beginning of pregnancy, the embryo possesses primordial germ cells in a way, precursors of gametes, oocytes or spermatozoa which, between 4 and 6 weeks of pregnancy, makes a long migration in the human body. They pass behind the future pancreas and arrive in the outline of the gonads, around the 7th week of pregnancy. Most likely, some of these germ cells stop on the way.
Researchers have developed a transcriptomic profile which identifies gene expression levels in a tissue of primordial germ cells at 6, 7, 11, 16 and 17 weeks of pregnancy, as well as of tumoral and healthy ovarian and pancreatic cells.
The researchers then compared these data, on one hand with the pancreas and on the other hand with the ovary, by studying for each of these two organs the profile of healthy tissues, mucinous tumours and other types of tumours. Their results are clear: in both cases, the transcriptomic profile of the mucinous tumour is far away from the supposed tissue of origin (ovary or pancreas), but very close to the primordial germ cells. This proves that these tumours are closer to the primordial germ cells than to the organ in which they developed.
Unexpected stops during migration
These results indicate that a stop in cell migration that occurred accidentally during the embryonic life of these women may, decades later, be expressed as cancer, depending on their other risk factors (e.g. smoking) and where in the body these primordial germ cells have settled. Indeed, while the scientists have examined the pancreas and ovary, similar cases have been reported everywhere on the migration line of germ cells, particularly in the liver or peritoneum.