Anal squamous cell carcinoma SCC will be diagnosed in an estimated 9, adults in the United States this year, and rates have been rising over the last several decades. To understand the sex-dependent differences, KC male mice were castrated and KC female mice were ovariectomized. Castrated KC males displayed an unchanged phenotype with no anal tumor formation.
Finally, exogenous administration of estrogen rescued the tumor development in ovariectomized KC female mice and induced tumor development in castrated KC males. These results confirm that the anal SCC is estrogen mediated. The delineation of the role of female sex hormones in mediating mutant Kras to drive anal SCC pathogenesis highlights a subtype of anal SCC that is independent of papillomavirus infection.
These findings may have clinical applicability for the papillomavirus-negative subset of anal SCC patients that typically respond poorly to standard of care chemoradiation.
This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: All relevant data are within the paper and its Supporting Information files. Competing interests: The authors have declared that no competing interests exist.
In , an estimated 9, adults will be diagnosed with anal squamous cell carcinoma SCC in the United States, and anal SCC has been increasing in incidence over the last several decades [ 1 , 2 ]. Despite this association, to our knowledge, the present study is the first to identify this correlation in a pre-clinical model. In this study, we found that Pdx1 expression and consequent Cre-recombinase expression in the anal epithelium caused activation of the Kras G12D gene in the anal epithelium and tumor development.
