title: The expression of FOXL2 in pancreatic, hepatobiliary, and renal tumors with ovarian-type stroma.
abstract: 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 expressed in normal ovarian stroma and ovarian neoplasms with granulosa cell lineage. Nonovarian tumors such as pancreatic mucinous cystic neoplasms (PMCs), hepatobiliary cystadenomas (HBCs), and mixed epithelial and stromal tumor of the kidney (MEST) have ovarian-type stroma. Immunohistochemical staining with FOXL2, estrogen receptor, and progesterone receptor was performed on 21 PMCs, 13 HBCs, and 10 MESTs and assessed for nuclear immunohistochemical positivity in the tumor stroma. All cases of PMC and HBC demonstrated nuclear reactivity for FOXL2 in the subepithelial stromal cells. Ninety percent of MEST demonstrated nuclear FOXL2 positivity. Estrogen receptor nuclear positivity was demonstrated in 57% of PMC, 77% of HBC, and 80% of MEST. Progesterone receptor nuclear positivity was present in 67% of PMC, 100% of HBC, and 90% of MEST. Clinical information was available for 37 patients. Seventy-eight percent of the patients had a history of obesity, heavy alcohol use, or hormone-related therapy. The 2 male patients had histories significant for morbid obesity and chronic alcoholism. 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. Most of such patients, including the rare male patients, have risk factors for hormonal abnormalities such as obesity and hormonal replacement therapy.
authors.affiliation: University of Washington Medical Center, Seattle, WA 98195. Electronic address: mwest2@uw.edu.
authors.forename: Maria
authors.initials: M
authors.lastname: Westerhoff
authors.affiliation: University of Washington Medical Center, Seattle, WA 98195.
authors.forename: Maria
authors.initials: M
authors.lastname: Tretiakova
authors.affiliation: University of Chicago Medical Center, Chicago, IL 60637.
authors.forename: John
authors.initials: J
authors.lastname: Hart
authors.affiliation: University of Chicago Medical Center, Chicago, IL 60637.
authors.forename: Katja
authors.initials: K
authors.lastname: Gwin
authors.affiliation: Cleveland Clinic, Cleveland, OH 809835.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Liu
authors.affiliation: New York University, New York, NY 10012.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.affiliation: University of Washington Medical Center, Seattle, WA 98195.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Yeh
authors.affiliation: University of Chicago Medical Center, Chicago, IL 60637.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Antic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000150:complications; D001650:Bile Duct Neoplasms / Q000503:physiopathology*; D003537:Cystadenoma / Q000503:physiopathology*; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D006801:Humans; D007680:Kidney Neoplasms / Q000503:physiopathology*; D008113:Liver Neoplasms / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D010190:Pancreatic Neoplasms / Q000503:physiopathology*; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone
keywords: FOXL2; Hepatobiliary cystadenoma; Mixed epithelial and stromal tumor of the kidney; Ovarian-type stroma; Pancreatic mucinous cystic neoplasm