Abstract MIP-074: CLUES FOR THE ORIGIN OF MUCINOUS OVARIAN TUMORS IN BRENNER TUMORS AND TERATOMAS?
Authors: Simons Michiel , Bulten Johan ,   PALGA Group, Massuger Leon F , Nagtegaal Iris D , Kurman Robert J 
Published: June 2017

Abstract
PURPOSE The origin of primary mucinous ovarian carcinomas is unknown. We investigated the possible relation between mucinous ovarian tumors and Brenner tumors and teratomas to identify the cell of origin, which might provide clues for future therapies.
EXPERIMENTAL PROCEDURES In total, 104 Brenner tumor-associated mucinous tumors (BAMT) and 58 teratoma-associated mucinous tumors (TAMT) were collected. All cases were revised and diagnosis, age, laterality, size, distributional pattern of Brenner nests and mucinous cysts, presence of mucinous metaplasia of Brenner nests, presence of mucinous stromal dissection and calcifications were scored. If the Fallopian tube was resected, presence of Walthard nests and transitional cell metaplasia was scored. On 37 BAMT and 24 TAMT, immunohistochem-istry for CK7, CK20, CDx2, HNF4α, SATB2, OC125, PAX-8, WT-1, p53, MUC4, CEA, ER, PR, Ki-67, PMS2, MSH2, MSH6, MLH1 and HER2 and Fluorescence In Situ Hybridization (FISH) for Her2/neu and c-Myc was performed. Also, Comparative Genomic Hybridization (CGH) for copy number analysis was carried out.
RESULTS Patients with TAMT were significantly younger than patients with BAMT (44.0 vs. 61.3 years respectively, p&lt;0.01). Mucinous stromal dissection occurred more often in TAMT (43% vs. 13%, p&lt;0.01), whereas in BAMT calcifications (56% vs. 22%, p&lt; 0.01) and Wal-thard cell nests (42% vs. 15%, p&lt;0.01) occurred more often. BAMT rarely expressed SATB2 (3% vs. 42%, p&lt;0.01). During progression from cystadenoma to atypical proliferative mucin-ous (borderline) tumor (APMT) to carcinoma in BAMT, there was a significant increase in expression of typical gastrointestinal markers CK20 (18%, 81%, 100%, p&lt;0.01), CDx2 (13%, 75%, 100%, p&lt;0.01), CEA (29%, 81%, 75%, p&lt;0.01) and HNF4 (71%, 100%, 100%, p=0.03). In TAMT, similar trends where observed without reaching statistical significance. For CK20, CDx2, HNF4α and MUC4 Brenner components showed no staining. WT-1 was positive in 47% of Brenner tumors, but only in 3% of associated mucinous tumors. All 3 tera-toma associated carcinomas showed wild type p53, in contrast to 3 out of 4 Brenner associat-ed carcinomas showing expression patterns matching mutated p53. Mismatch repair protein expression was normal in all carcinomas. One Brenner tumor associated carcinoma and one teratoma associated APMT showed positive Her2/neu status. No Brenner tumors were posi-tive for Her2/neu. No c-Myc amplification was noted. Results of CGH are pending.
CONCLUSION Teratomas and Brenner tumors give rise to different subtypes of mucinous ovarian tumors, with different demographic and histological presentation. Remarkably, both TAMT and BAMT progress to a gastrointestinal phenotype, suggesting the commonly applied routine immunohistochemistry a poor tool for detection of origin.
Citation Format: Michiel Simons, Johan Bulten, PALGA Group, Leon F Massuger, Iris D Nagtegaal, Robert J Kurman. CLUES FOR THE ORIGIN OF MUCINOUS OVARIAN TUMORS IN BRENNER TUMORS AND TERATOMAS? [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr MIP-074.