Expression of Embryonic Markers in Endometrial Epitheliium: A Unique Topography with Implications for Tumorigenesis
Brooke E Howitt, Michael Herfs, Gang Ning, Christopher P Crum. Brigham and Women's Hospital, Boston, MA; University of Liege, Liege, Belgium; Jackson Laboratory, Farmington, CT
Background: We have previously shown that Krt7 is expressed in embryonic mullerian epithelium, identifiesthe squamocolumnar junction (SCJ), cancers and precursor lesions in the cervix. This study investigated expression of Krt7 in the uterus during development, reproductive life and in neoplasia. The goal was to determine if a parallel existed in the endometrium and if expression patterns correlated with tumor type.
Design: Sections of human and murine uteri in early development were stained with Krt7. Cases were evaluatedfor the distribution of Krt7 expression and its topographic relationship to the surface epithelium and subjacent endometrial glands. In addition endometrial samples including polyps, 13 grade 1-2 and two grade 3 endometrioid endometrial adenocarcinomas and six uterine serous carcinomas were stained.
Results: During development, Krt7 in both the human (20 weeks) and mouse (6 days post natal) intensely stained the surface epithelial cells lining the uterine cavity. With the onset of subjacent gland formation, Krt7 expression diminished, in parallel with the reduction in staining seen in the endocervical epithelium away from the squamocolumnar junction. During reproductive life, staining was retained on the surface. 5/6 serous carcinomas and one grade 3 endometrioid carcinoma were strongly Kr7+. In contrast, all 13 grade 1 or 2 endometrioid carcinomas were either negative or showed heterogenous staining.
Conclusions: The uterine surface lining is immunophenotypically distinct from the endometrial glands and shares identity with embryonic epithelium in keeping with a role as epithelial progenitor. The emergence of Krt7- glands from this epithelium during development, and persistence of these glands into adulthood underscore the differences between the two epithelial compartments and suggest that the surface epithelium harbors the stem cells required for regeneration. Differences in Krt7 expression in uterine serous and endometrioid carcinomas imply that these tumors may arise from different cell types; a concept reinforced by the superficial nature of early serous carcinomas and the fact that endometrioid neoplasms are predominately gland forming. The potential for these markers to augment current endometrial tumor classifications based on site or cell of origin merits further investigation.
Category: Gynecologic & Obstetrics
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 129, Tuesday Morning