SIX1 Expression in Human Fetal Tissues
Rong Rong, Li-Ping Wang, Elizabeth Ruckdeschel, Zhanyong Bing. University of Pennsylvania, Philadelphia, PA; Upstate Medical University, Syracuse, NY
Background: SIX1 is a key regulator of Epithelial-Mesenchymal transition (EMT), a cellular process that plays a major role in normal organ development and tumor progression. Congenital mutations of SIX1 gene have been identified in patients with Branchio-oto-renal syndrome, a development disorder characterized by hearing loss, branchial arch defects and renal anomalies. Overexpression of SIX1 correlates with adverse outcome in a variety of human tumors. In breast and colorectal cancer SIX1 has been shown to promote carcinogenesis and tumor progression through the induction of EMT. Although the expression of SIX1 during embryogenesis has been studied in mouse models in order to better understand its physiological role, the expression of SIX1 in human fetal tissue has not been systematically evaluated.
Design: We evaluated the expression of SIX1 in multiple fetal tissues including brain, heart, lung, kidney, adrenal gland, liver and small bowel. Twenty three archived human fetal tissue specimens were collected from the Dept. of Pathology at the University of Pennsylvania between 12/16/09 and 7/26/12. The gestational ages range from 15 to 21 weeks. Immunohistochemical staining for SIX1 was performed on paraffin-embedded tissue sections using rabbit polyclonal anti-SIX1 antibody.
Results: SIX1 is highly expressed in the subcapsular zone of the kidney. The strongest staining is noted in the metanephric mesenchyme surrounding the ureteric buds. As the metanephric mesenchyme undergoes mesenchymal to epithelial transition (the reverse process of EMT) and forms the renal vesicles, the staining of SIX1 is gradually reduced. Unlike previous findings in mouse models, there is minimal staining of SIX1 in the renal tubule epithelium. In the canalicular stage of fetal lung development, SIX1 shows strong staining in a subpopulation of bronchial tree epithelial cells, and moderate staining in terminal bronchiole, alveolar duct epithelium and scattered mesenchymal cells. In contrast, SIX1 has been shown to be specifically expressed in distal lung mesenchyme and epithelium in mouse embryos of similar gestational stage. In the remainder of the tissues examined, the staining of SIX1 is significantly weaker, the significance of which is unclear.
Conclusions: Our study demonstrates for the first time that SIX1 staining patterns differ between the human fetus and the mouse embryo of comparable gestational stage. We found that SIX1 is highly expressed in kidney and lung from second trimester human fetuses. Its expression is seen in both mesenchymal and epithelial cells.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 282, Monday Morning