PAX2-Null Secretory Cell Outgrowths (SCOUTs) in the Fallopian Tube Comprise Two Distinct Subgroups
Jonathan G Bijron, Christopher P Crum, Frank D McKeon, Wa Xian, Gang Ning. Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA; Institute of Medical Biology, A*STAR, Singapore
Background: The fallopian tube hosts precursor and precursor-like entities known as secretory cell outgrowths (SCOUTs). These SCOUTs are typically PAX2-null and have a higher frequency as a function of older age and are increased in women with serous carcinoma. Although they are described as secretory in nature, we have identified additional patterns of differentiation in SCOUTs. This report describes a study in which SCOUTs were catalogued and classified according immunophenotype.
Design: Fallopian tube sections from 23 patients were stained with PAX2 and the presence of PAX2-null SCOUTs determined. Sections containing PAX2-null SCOUTs were then immunostained with markers for both secretory (PAX8) and ciliated (tubulin) cell differentiation. Attention was paid to histopathology suggesting either differentiation pathway and immunophenotype. In addition, SCOUTs were immunostained with a set of three markers that we have been recently associated with SCOUTs, including β-catenin, LEF1 and ALDH1.
Results: Sixty-eight PAX2-null SCOUTs were identified. Of these 45 (66%) showed the presence of ciliated cells within an otherwise predominantly secretory population. Secondly, 25 (36.7%) were positive for the selected markers. Two groups of SCOUTs emerged based on differentiation and could be further subdivided according to the biomarker panel; Type I were devoid of ciliation and included Type IA (markers+/ciliation-) and Type IB (markers-/ciliation-). Type II contained ciliation and included Type IIA (markers+/ciliation+) and type IIB (markers-/ciliation+). Type II showed mixed ciliated and secretory differentiation with patterns of columnar cell shape (type IIa) and stratified, papillary shaped epithelium (type IIb). Type II SCOUTs tended to be larger, often showing a mild papillary architecture.
Conclusions: We have found two subsets of SCOUTs that exhibit both differences in differentiation and gene expression. The fact that these oviductal cell expansions differ in their capacity to generate ciliated differentiation raises the distinct possibility that they signify perturbations of two different differentiation pathways and perhaps different cells of origin. Because genes altered in this process are often perturbed in serous cancers we propose that progressive functional gene alterations in oviductal epithelium occur with age and may reflect an accumulation of risk-associated molecular events germane to not only the oviduct but in other Mullerian epithelium.
Category: Gynecologic & Obstetrics
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 187, Tuesday Morning