| Literature DB >> 31239549 |
Nicola S Meagher1,2,3, Linyuan Wang4, Peter F Rambau4,5, Maria P Intermaggio1,3, David G Huntsman6,7,8, Lynne R Wilkens9, Mona A El-Bahrawy10, Roberta B Ness11, Kunle Odunsi12, Helen Steed13, Esther Herpel14,15, Michael S Anglesio8, Bonnie Zhang16, Neil Lambie17, Anthony J Swerdlow18,19, Jan Lubiński20, Robert A Vierkant21, Ellen L Goode22, Usha Menon23, Aleksandra Toloczko-Grabarek20, Oleg Oszurek24, Sanela Bilic16, Aline Talhouk6, Montserrat García-Closas25,26, Qin Wang27, Adeline Tan28,29, Rhonda Farrell30, Catherine J Kennedy31,32, Mercedes Jimenez-Linan33, Karin Sundfeldt34,35, John L Etter36, Janusz Menkiszak37, Marc T Goodman38,39, Paul Klonowski4, Yee Leung40, Stacey J Winham21, Kirsten B Moysich36, Sabine Behrens41, Tomasz Kluz42, Robert P Edwards43,44, Jacek Gronwald20, Francesmary Modugno44,45, Brenda Y Hernandez46, Christine Chow47, Linda E Kelemen48, Gary L Keeney49, Michael E Carney50, Yanina Natanzon22, Gregory Robertson1,51, Raghwa Sharma52,53, Simon A Gayther54,55,56, Jennifer Alsop57, Hugh Luk9, Chloe Karpinskyj58, Ian Campbell59,60, Peter Sinn15, Aleksandra Gentry-Maharaj58, Penny Coulson26, Jenny Chang-Claude41,61, Mitul Shah57, Martin Widschwendter58, Katrina Tang17, Minouk J Schoemaker18, Jennifer M Koziak62, Linda S Cook63,64, James D Brenton65, Frances Daley66,67, Björg Kristjansdottir34,35, Constantina Mateoiu68, Melissa C Larson21, Paul R Harnett31,69, Audrey Jung41, Anna deFazio31,32, Kylie L Gorringe59, Paul D P Pharoah27,57, Parham Minoo4, Colin Stewart40, Oliver F Bathe70, Xianyong Gui4, Paul Cohen16,28, Susan J Ramus1,3,71, Martin Köbel72.
Abstract
Primary ovarian mucinous tumors can be difficult to distinguish from metastatic gastrointestinal neoplasms by histology alone. The expected immunoprofile of a suspected metastatic lower gastrointestinal tumor is CK7-/CK20+/CDX2+/PAX8-. This study assesses the addition of a novel marker SATB2, to improve the diagnostic algorithm. A test cohort included 155 ovarian mucinous tumors (105 carcinomas and 50 borderline tumors) and 230 primary lower gastrointestinal neoplasms (123 colorectal adenocarcinomas and 107 appendiceal neoplasms). All cases were assessed for SATB2, PAX8 CK7, CK20, and CDX2 expression on tissue microarrays. Expression was scored in a 3-tier system as absent, focal (1-50% of tumor cells) and diffuse ( >50% of tumor cells) and then categorized into either absent/present or nondiffuse/diffuse. SATB2 and PAX8 expression was further evaluated in ovarian tumors from an international cohort of 2876 patients (expansion cohort, including 159 mucinous carcinomas and 46 borderline mucinous tumors). The highest accuracy of an individual marker in distinguishing lower gastrointestinal from ovarian mucinous tumors was CK7 (91.7%, nondiffuse/diffuse cut-off) followed by SATB2 (88.8%, present/absent cut-off). The most effective combination was CK7 and SATB2 with accuracy of 95.3% using the 3-tier interpretation, absent/focal/diffuse. This combination outperformed the standard clinical set of CK7, CK20 and CDX2 (87.5%). Re-evaluation of outlier cases confirmed ovarian origin for all but one case. The accuracy of SATB2 was confirmed in the expansion cohort (91.5%). SATB2 expression was also detected in 15% of ovarian endometrioid carcinoma but less than 5% of other ovarian histotypes. A simple two marker combination of CK7 and SATB2 can distinguish lower gastrointestinal from ovarian primary mucinous tumors with greater than 95% accuracy. PAX8 and CDX2 have value as second-line markers. The utility of CK20 in this setting is low and this warrants replacement of this marker with SATB2 in clinical practice.Entities:
Mesh：
Substances：
Year: 2019 PMID： 31239549 PMCID： PMC8207534 DOI： 10.1038/s41379-019-0302-0
Source DB: PubMed Journal: Mod Pathol ISSN： 0893-3952 Impact factor: 8.209