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A combination of the immunohistochemical markers CK7 and SATB2 is highly sensitive and specific for distinguishing primary ovarian mucinous tumors from colorectal and appendiceal metastases

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Title: A combination of the immunohistochemical markers CK7 and SATB2 is highly sensitive and specific for distinguishing primary ovarian mucinous tumors from colorectal and appendiceal metastases
Authors: Meagher, NS
Wang, L
Rambau, PF
Intermaggio, MP
Huntsman, DG
Wilkens, LR
El-Bahrawy, MA
Ness, RB
Odunsi, K
Steed, H
Herpel, E
Anglesio, MS
Zhang, B
Lambie, N
Swerdlow, AJ
Lubinski, J
Vierkant, RA
Goode, EL
Menon, U
Toloczko-Grabarek, A
Oszurek, O
Bilic, S
Talhouk, A
Garcia-Closas, M
Wang, Q
Tan, A
Farrell, R
Kennedy, CJ
Jimenez-Linan, M
Sundfeldt, K
Etter, JL
Menkiszak, J
Goodman, MT
Klonowski, P
Leung, Y
Winham, SJ
Moysich, KB
Behrens, S
Kluz, T
Edwards, RP
Gronwald, J
Modugno, F
Hernandez, BY
Chow, C
Kelemen, LE
Keeney, GL
Carney, ME
Natanzon, Y
Robertson, G
Sharma, R
Gayther, SA
Alsop, J
Luk, H
Karpinskyj, C
Campbell, I
Sinn, P
Gentry-Maharaj, A
Coulson, P
Chang-Claude, J
Shah, M
Widschwendter, M
Tang, K
Schoemaker, MJ
Koziak, JM
Cook, LS
Brenton, JD
Daley, F
Kristjansdottir, B
Mateoiu, C
Larson, MC
Harnett, PR
Jung, A
DeFazio, A
Gorringe, KL
Pharoah, PDP
Minoo, P
Stewart, C
Bathe, OF
Gui, X
Cohen, P
Ramus, SJ
Kobel, M
Item Type: Journal Article
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.
Issue Date: 25-Jun-2019
Date of Acceptance: 18-May-2019
URI: http://hdl.handle.net/10044/1/89511
DOI: 10.1038/s41379-019-0302-0
ISSN: 0893-3952
Publisher: Springer Nature [academic journals on nature.com]
Start Page: 1834
End Page: 1846
Journal / Book Title: Modern Pathology
Volume: 32
Issue: 12
Copyright Statement: © The Author(s), under exclusive licensc to United States & Canadian Academy of Pathology 2019. The final publication is available at Springer via https://doi.org/10.1038/s41379-019-0302-0
Keywords: Science & Technology
Life Sciences & Biomedicine
Pathology
EXPRESSION
CARCINOMA
CDX2
DISTINCTION
ADENOCARCINOMA
NEOPLASMS
PROFILES
SURVIVAL
CANCERS
SERIES
Adenocarcinoma, Mucinous
Appendiceal Neoplasms
Biomarkers, Tumor
Colorectal Neoplasms
Diagnosis, Differential
Female
Humans
Immunohistochemistry
Keratin-7
Male
Matrix Attachment Region Binding Proteins
Neoplasm Metastasis
Ovarian Neoplasms
Sensitivity and Specificity
Transcription Factors
Humans
Adenocarcinoma, Mucinous
Appendiceal Neoplasms
Colorectal Neoplasms
Ovarian Neoplasms
Neoplasm Metastasis
Matrix Attachment Region Binding Proteins
Transcription Factors
Diagnosis, Differential
Immunohistochemistry
Sensitivity and Specificity
Female
Male
Keratin-7
Biomarkers, Tumor
Science & Technology
Life Sciences & Biomedicine
Pathology
EXPRESSION
CARCINOMA
CDX2
DISTINCTION
ADENOCARCINOMA
NEOPLASMS
PROFILES
SURVIVAL
CANCERS
SERIES
Pathology
11 Medical and Health Sciences
Publication Status: Published
Online Publication Date: 2019-06-25
Appears in Collections:Department of Metabolism, Digestion and Reproduction