New insights into the development and differentiation of the human anorectal epithelia. Are there clinical consequences?

Abstract

PurposeThe epithelial lining of the anorectum still raises discussions concerning the levels of transition between the various zones and leads to an incomplete understanding of the immmunoprofile of rectal carcinoma. Since the expression of cytokeratins depends on the epithelial cell-type and the parahox-gene CDX2 is important for the development of the colorectal epithelium, we investigated different cytokeratins and CDX2 in the anorectum of human prenatal stages and in adult normal and neoplastic anorecta.Materials and MethodsThe differentiation and spatiotemporal distribution of the epithelial zones were examined in 33 human embryos and fetuses, in a 2-year-old child and four adults. In comparison, 17 specimens of ultralow rectal adenocarcinoma and 4 specimens of anal carcinoma were investigated. Monoclonal antibodies were directed against cytokeratin (CK) 18, 20, 7 and 14 and CDX2.ResultsDue to the cytokeratin profile and to CDX2 expression, the different anorectal zones could already be differentiated in human prenatal life. We showed that anorectal epithelial differentiation including the squamous epithelia ran in a craniocaudal direction, and that the anorectal zone was a transitional zone between rectal zone and anal transitional zone where CK 7, 18, 20 and CDX2 are simultaneously expressed. All cases of rectal adenocarcinoma showed positivity for CK 18, 20 and CDX2, and three also labelled for CK 7, whereas CK 14 was only expressed in the cases of anal carcinoma.ConclusionsOur results elucidate the connection between the prenatal pattern and the origin of the different types of anorectal carcinoma.

Development of epithelial and mesenchymal regionalization of the human fetal utero‐vaginal anlagen

“…The specimens, which had already been investigated in other studies (Fritsch et al. ), showed no macroscopic abnormalities and were categorized according to their postovulatory age (O'Rahilly & Müller, ), which was based upon the crown–rump length (CRL) and external and internal morphology, or upon their estimated gynaecological age.…”

“…The specimens were obtained from the archival collection of the Division of Clinical and Functional Anatomy, Innsbruck Medical University (number of specimens/week: 3/14th, 4/15th, 3/16th, 3/17th, 1/19th, 2/20th, 1/21st, 2/ 24th, 2/25th, 2/29th, 1/30th and 2/newborn). The specimens, which had already been investigated in other studies (Fritsch et al 2010), showed no macroscopic abnormalities and were categorized according to their postovulatory age (O'Rahilly & M€ uller, 2010), which was based upon the crown-rump length (CRL) and external and internal morphology, or upon their estimated gynaecological age.…”

Anatomical considerations for transanal minimal‐invasive surgery: the caudal to cephalic approach

“…The surgical ‘no‐man's land’ at the anorectal junction is part of the ultralow portion of the distal third of the rectum . It is derived from the cloacal part of the hindgut and can be interpreted as a specialized ‘sensory organ’ characterised by the loss of mesorectum with the lymphatics, the blood supply and specialized innervation running intramurally. A dense network of intrinsic autonomic ganglia (plexus myentericus and submucosus), cell abundance and afferent as well as efferent nerve fibres can be found in this region and constitute the extrinsic autonomic nerve system (inferior rectal branches ; Fig.…”

Is CDX2 immunostaining useful for delineating anorectal from penile/vulvar squamous cancer in the setting of squamous cell carcinoma with clinically unknown primary site presenting with histologically confirmed inguinal lymph node metastasis?

“…In particular, given that nuclear CDX2 expression has been immunohistochemically confirmed to occur in the human ARZ, it is tempting to speculate that SCCs derived from the ARZ might retain CDX2 expression, while their counterparts originating from the ATZ, SZ or perianal skin might not show CDX2 expression 6. However, this speculation remains to be proven by advanced studies in the future.…”