Anti-FOXL2 Antibody Is a Sensitive and Specific Diagnostic Marker for Ovarian Sex Cord-Stromal Tumors.
Osama M Al-Agha, Hassan F Huwait, Christine Chow, Winnie Yang, Janine E Senz, Steve G Kalloger, David H Huntsman, Robert Young, C Blake Gilks. British Columbia Cancer Agency and Vancouver General Hospital, Vancouver, Canada; Massachusetts General Hospital, Boston
Background: We recently identified FOXL2 (402C→G) mutation as being characteristic in adult granulosa cell tumor (aGCT). Testing for this aGCT-specific mutation is not widely available. Therefore, we assessed the potential diagnostic utility of FOXL2 immunostaining by examining the immunohistochemical expression of FOXL2 protein in a broad range of ovarian tumors.
Design: Using a commercially available polycloncal antiserum against FOXL2 protein (Imgenex 1:25 dilution), immunoexpression of FOXL2 was analysed in 501 ovarian tumors, including 130 SCST, using whole tissue sections and tissue microarrays. Immunostaining was also correlated with FOXL2 mutation status. In addition, we compared FOXL2 immunoexpression with that of alpha-inhibin and calretinin in a subset of 89 SCST.
Results: There was positive nuclear staining for FOXL2 in 99/501 (19.8%) cases. FOXL2 immunostaining was present in 96 of 130 (74%) SCST, including more than 95% of aGCT, juvenile granulosa cell tumors, fibromas, and sclerosing stromal tumors. Only 50% (20/40) of Sertoli-Leydig cell tumors (SLCT) stained for FOXL2. Three of three (100%) female adnexal tumors of probable Wolffian origin showed FOXL2 immunoreactivity, while all other non-SCST tested (n=368) were completely negative for FOXL2. Forty five of 130 (34.6%) SCST were positive for FOXL2 (402C→G) mutation, including 39/42 (93%) aGCT, 3 of 40 (7.5%) SLCT, 2 of 5 (40%) thecomas, and 1 of 4 (25%) sex cord-stromal tumors of unclassified type. SCST with a FOXL2 mutation consistently immunoexpressed FOXL2 (44 of 45, 98%), but FOXL2 immunostaining was also seen in many SCST that lacked a mutation (50 of 85, 62.5%). FOXL2 immunostaining showed higher sensitivity for SCST (74%), compared to calretinin (66%), and alpha-inhibin (57%). In the FOXL2-immunonegative SCST, alpha-inhibin and/or calretinin immunostaining yielded positive results in every case.
Conclusions: FOXL2 is a novel immunohistochemical marker that is both sensitive and specific for SCST. FOXL2 immunostaining is present in almost all SCST with a FOXL2 mutation, as well as a majority of SCST without a mutation. The use of FOXL2 together with alpha-inhibin and/or calrentinin should form a panel that yields positive staining with one or more marker in essentially all cases of SCST. Because FOXL2 immunostaining does not generally distinguish among tumors within SCST category, genetic testing for aGCT-specific FOXL2 (402C→G) mutation remains the only diagnostic tool to separate aGCT from other SCST.
Category: Gynecologic & Obstetrics
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 143, Monday Morning