We read with great interest the article by Pissetti et al[1] entitled ‘Gene Polymorphisms in FAS (Rs3740286 and Rs4064) Are Involved in Endometriosis Development in Brazilian Women,
but not those in CASP8 (rs13416436 and rs2037815),’ published in your journal. The authors investigated
the association between two polymorphisms involved in apoptosis and the risk of developing
endometriosis in a case-control study enrolling 45 women. Interestingly, they found
a positive association between polymorphisms of the Fas cell surface death receptor
gene FAS and the confirmed surgical diagnosis of endometriosis.
The authors investigated polymorphisms of the FAS gene, similarly to other previous authors.[2] Overall, one of the alterations appearing in the eutopic and ectopic endometria
of women with endometriosis refers to the regulation of apoptosis. In fact, anomalous
susceptibility of endometrial tissue to apoptosis may deeply contribute to the development
of implants[3]; in particular, it has been reported that expressions of FAS and its ligand may be decreased in eutopic and ectopic endometria of women with endometriosis.[4] In contrast, higher levels of proapoptotic proteins, such as FAS ligand, in the peritoneal fluid of women with endometriosis may contribute to an
increased apoptosis of immune cells, leading to decreased scavenger activity in the
peritoneal cavity and, thus, less immune clearance.[5]
Pissetti et al[1] should be congratulated for their laboratory findings regarding a controversial
and complex topic. In any case, we would be glad to make some considerations on this
interesting study. First, it would be of particular interest to know if the presence
of these polymorphisms would be different in patients with implants originating from
peritoneal nodules, ovarian endometriomas or deep infiltrating endometriosis, three
distinguished phenotypes of endometriosis that are known to have probably different
pathogeneses.[6] In relation to this, it has been previously supposed that apoptosis could especially
contribute to the survival of endometrial cells regurgitated in the peritoneal cavity
and the subsequent development of peritoneal endometriotic implants.[3]
Although the authors correctly reported the distribution of the different endometriosis
stages in the patients' population, according to the American Society for Reproductive
Medicine (ASRM) classification, it would be interesting to know if there has been
a specific correlation between FAS genetic polymorphisms and a higher median endometriosis stage or a worse patients'
clinical symptomatology.
In conclusion, the role of apoptosis in endometriosis appears to be an attractive
topic; in the near future, this pathway may represent a suitable target for treatment
of this disease, which needs a chronic therapy balancing clinical efficacy with tolerability.[7] In support of this view, in a recent narrative review, we found preclinical experiments
in vitro and in animal models focalized on drugs acting on apoptosis.[8] Furthermore, as stated by the authors, the investigation of these polymorphisms
as biomarkers to determine predisposition and prognosis for endometriosis appears
another fascinating opportunity.
