The Expression of FOXL2 in Pancreatic, Hepatobiliary, and Renal Tumors with Ovarian-Type Stroma.
Maria Westerhoff, Maria Tretiakova, Lindsey Hovan, John Hart, Katja Gwin, Tatjana Antic. University of Chicago, IL
Background: FOXL2, a gene encoding a member of the fork-head-winged-helix family of transcription factors, is one of the earliest expressed genes during female gonadal development. It is required for folliculogenesis and is expressed in ovarian stroma. FOXL2 also opposes testicular development by suppressing the counteracting transcription factor SOX9. Moreover, FOXL2 is expressed in ovarian neoplasms with granulosa cell lineage.
Non-ovarian tumors such as pancreatic mucinous cystic neoplasms (PMC), hepatobiliary cystadenomas (HBC), and renal mixed epithelial stromal tumors (MEST), share the distinctive feature of having ovarian-type stroma. Given the expression of FOXL2 in normal human ovaries, the aim of our study was to further characterize the stroma in these non-ovarian tumors.
Design: 20 PMC, 5 HBC, and 3 MEST were retrieved from the surgical pathology database. H&E sections were reviewed and immunohistochemical (IHC) staining with FOXL2 (goat IgG, IMAENEX), estrogen receptor (ER), and progesterone receptor (PR) were assessed for nuclear IHC positivity in the tumor stroma.
Results: There were 26 females and 2 males (both PMC), with an age range of 35-71 years. All cases (20/20 PMC, 3/3 MEST, and 5/5 HBC) demonstrated strong nuclear reactivity for FOXL2 in the subepithelial stromal cells. ER and PR demonstrated nuclear reactivity in 12/20 PMC, 2/3 MEST, and 4/5 HBC, but staining intensity was generally weaker and patchier. The sensitivity of FOXL2 (100%) was superior to that of ER and PR (64%).
Clinical information was available for 20 patients. In 17/20 there was a history of obesity, chronic tamoxifen use, or oral contraceptive use. The 2 male patients had histories significant for morbid obesity and chronic alcoholism.
Conclusions: FOXL2 is expressed from the early stages of ovarian development and has been shown to be mandatory for normal ovarian function. We have shown that it is also expressed in the aberrant ovarian-type stroma characteristic of PMC, HBC, and MEST. It is more sensitive than ER and PR in demonstrating the stromal elements by IHC. The majority of such patients, including the rare male patients, have risk factors for hormonal abnormalities, such as morbid obesity and hormonal replacement therapy. There is no well-delineated explanation for the presence of ovarian-type stroma in PMC, HBC, and MEST. FOXL2 may be useful not only as an adjunct diagnostic marker, but in the elucidation of the embryologic origin/pathogenesis of the stroma in these tumors.
Category: Liver & Pancreas
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 195, Tuesday Afternoon