Brenner Tumors. A Mutational and Immunohistochemical Analysis of 39 Cases
Elisabetta Kuhn, Tian-Li Wang, Jeffrey D Seidman, Ie-Ming Shih, Robert J Kurman. Johns Hopkins Medical Institutions, Baltimore, MD; Washington Hospital Center, Washington, DC
Background: Benign Brenner tumors (BTs) are classified as epithelial tumors of the ovary, based on the presence of nests of epithelial cells resembling urothelium. They are thought to be derived from Walthard cell nests because of their similar appearance. In addition, they have a prominent fibromatous stroma. The aim of this study was to evaluate their immunohistochemical and molecular genetic features with the view that this might shed light on their pathogenesis.
Design: A total of 39 BTs were retrieved from the Johns Hopkins Hospital and the Washington Hospital Center surgical pathology files. Immunohistochemistry (IHC) for WT1, ER, PR, calretinin, SF1 and alpha-inhibin was performed on FFPE tissue sections on 39 tumors. In addition, the nests of transitional-type epithelium from 20 tumors were laser-capture microdissected. The stromal component was manually microdissected in all cases as well. Genomic DNA was extracted for sequence analysis of BRAF, KRAS, PIK3CA, CTNNB1, HER2, PPP2R1A and FOXL2 mutations.
Results: A somatic mutation of PIK3CA was detected in the stromal component in one tumor. No other mutations were detected in either the epithelial or the stromal component in the remaining tumors. IHC analysis revealed weak WT1 immunoreactivity in the epithelial nests in 3 cases. A similar IHC pattern of WT1 was found in the stromal cell component in 12 cases. In contrast, there was weak expression of ER in 28/39 (72%) and PR in 26/39 (67%), and strong expression of calretinin in 36/39 (92%), SF1 in 37/39 (95%) and alpha-inhibin in 34/39 (87%) in the stromal component. In contrast, expression of these biomarkers in the epithelial component was generally absent. Notably, calretinin, SF1 and alpha-inhibin showed particularly strong staining in the stromal cells that immediately surrounded the epithelial nests in the majority of the tumors.
Conclusions: Our findings suggest that mutation of the genes analyzed is unlikely to be a common molecular genetic aberration underlying the development of BTs. Moreover, the periepithelial IHC pattern of calretinin, SF1 and alpha-inhibin, markers of steroidogenic cells, suggests that the stroma is not a passive component but may play an important role in the pathogenesis of this tumor. It is conceivable that the stroma is responsible for inducing the epithelium or vice versa. Further studies are necessary to identify common molecular genetic aberrations in this tumor.
Category: Gynecologic & Obstetrics
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 189, Monday Morning