{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T10:50:54Z","timestamp":1773312654573,"version":"3.50.1"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:p>Primary mucinous ovarian neoplasms, gastrointestinal-type (GI-type), are composed of mucin-producing tumor cells resembling intestinal goblet cells or gastric foveolar epithelium. In contrast to seromucinous tumors, which exhibit endocervical-type mucinous differentiation and are thought to be derived from endometriosis, the cell\/tissue-of-origin of most GI-type mucinous ovarian tumors is unknown. We identified 8 GI-type mucinous ovarian tumors (cystadenomas, n=4; borderline tumor\/carcinoma, n=4) with spatially distinct areas that showed morphologic features of Mullerian-type epithelial differentiation (ciliated cells or endometrioid-type glands). Immunohistochemistry for cell lineage markers and Alcian blue (pH 2.5)\/Periodic Acid-Schiff staining were performed. Morphologically distinct components were isolated by microdissection, from which extracted DNA was analyzed by targeted next-generation sequencing. In all cases, immunohistochemistry demonstrated mucin-producing cells to be positive for at least one GI marker (CK20 or CDX2), while areas with morphologic features of Mullerian differentiation were positive for PAX8, ER and\/or PR, and lacked expression of CK20 and CDX2; CK7 was strongly and diffusely positive in all tumor cells. Tumor cells with a gastric-type phenotype produced neutral mucin, while acidic mucin was present within intestinal-type goblet cells. Targeted sequencing revealed <jats:italic toggle=\"yes\">ARID1A<\/jats:italic> mutations in all mixed borderline tumors\/carcinomas (n=4); other recurrent genetic alterations included <jats:italic toggle=\"yes\">KRAS<\/jats:italic> (n=2) and <jats:italic toggle=\"yes\">TP53<\/jats:italic> mutations (n=2). Shared mutations were present in paired Mullerian and GI-type mucinous tumor components in 4 mixed borderline tumors\/carcinomas, with more shared mutations between components than private mutations specific to each component. All mixed borderline tumors\/carcinomas were associated with endometriosis (n=3) or Mullerian inclusion cysts (n=1); mutation or loss of ARID1A expression was seen in these putative precursor lesions in 2 cases. Hence, ovarian neoplasms composed of clonally related GI-type mucinous and Mullerian-type epithelial components harbor <jats:italic toggle=\"yes\">ARID1A<\/jats:italic> mutations and are frequently associated with endometriosis. The existence of a Mullerian stem\/progenitor cell with the capacity to differentiate toward cell lineages within the GI-tract may be involved in the pathogenesis of at least a subset of GI-type mucinous ovarian neoplasms.<\/jats:p>","DOI":"10.1097\/pas.0000000000002045","type":"journal-article","created":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T09:00:06Z","timestamp":1682931606000},"page":"756-765","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":4,"title":["Mixed Ovarian Neoplasms With Gastrointestinal-type Mucinous and Mullerian Epithelial Components"],"prefix":"10.1097","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7220-3996","authenticated-orcid":false,"given":"Michael Herman","family":"Chui","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lora H.","family":"Ellenson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2023,5,1]]},"reference":[{"key":"R2-20250608","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/path.5545","article-title":"Genomic analysis of low-grade serous ovarian carcinoma to identify key drivers and therapeutic vulnerabilities","volume":"253","author":"Cheasley","year":"2021","journal-title":"J Pathol"},{"key":"R3-20250608","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s13073-015-0210-y","article-title":"Mutational landscape of mucinous ovarian carcinoma and its neoplastic precursors","volume":"7","author":"Ryland","year":"2015","journal-title":"Genome Med"},{"key":"R5-20250608","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1097\/PGP.0000000000000266","article-title":"Seromucinous tumors of the ovary. 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