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

Ovarian Cancer Association Consortium

Research output: Contribution to journalArticle

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.
Original languageEnglish
Number of pages13
JournalModern Pathology
DOIs
Publication statusPublished - 25 Jun 2019

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Colorectal Neoplasms
Neoplasm Metastasis
Neoplasms
Gastrointestinal Neoplasms
Appendiceal Neoplasms
Endometrioid Carcinoma
Mucinous Adenocarcinoma
Histology
Adenocarcinoma
Carcinoma

Cite this

@article{6ce06e51d2c84c6a89fb11bc290a9d4f,
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",
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.",
author = "{Ovarian Cancer Association Consortium} and Meagher, {Nicola S.} and Linyuan Wang and Rambau, {Peter F.} and Intermaggio, {Maria P.} and Huntsman, {David G.} and Wilkens, {Lynne R.} and El-Bahrawy, {Mona A.} and Ness, {Roberta B.} and Kunle Odunsi and Helen Steed and Esther Herpel and Anglesio, {Michael S.} and Bonnie Zhang and Neil Lambie and Swerdlow, {Anthony J.} and Jan Lubiński and Vierkant, {Robert A.} and Goode, {Ellen L.} and Usha Menon and Aleksandra Toloczko-Grabarek and Oleg Oszurek and Sanela Bilic and Aline Talhouk and Montserrat Garc{\'i}a-Closas and Qin Wang and Adeline Tan and Rhonda Farrell and Kennedy, {Catherine J.} and Mercedes Jimenez-Linan and Karin Sundfeldt and Etter, {John L.} and Janusz Menkiszak and Goodman, {Marc T.} and Paul Klonowski and Yee Leung and Winham, {Stacey J.} and Moysich, {Kirsten B.} and Sabine Behrens and Anna deFazio and Gorringe, {Kylie L.} and Pharoah, {Paul D. P.} and Colin Stewart and Paul Cohen and Ramus, {Susan J.} and Martin K{\"o}bel",
year = "2019",
month = "6",
day = "25",
doi = "10.1038/s41379-019-0302-0",
language = "English",
journal = "Modern Pathology",
issn = "0893-3952",
publisher = "Nature Publishing Group - Macmillan Publishers",

}

TY - JOUR

T1 - 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

AU - Ovarian Cancer Association Consortium

AU - Meagher, Nicola S.

AU - Wang, Linyuan

AU - Rambau, Peter F.

AU - Intermaggio, Maria P.

AU - Huntsman, David G.

AU - Wilkens, Lynne R.

AU - El-Bahrawy, Mona A.

AU - Ness, Roberta B.

AU - Odunsi, Kunle

AU - Steed, Helen

AU - Herpel, Esther

AU - Anglesio, Michael S.

AU - Zhang, Bonnie

AU - Lambie, Neil

AU - Swerdlow, Anthony J.

AU - Lubiński, Jan

AU - Vierkant, Robert A.

AU - Goode, Ellen L.

AU - Menon, Usha

AU - Toloczko-Grabarek, Aleksandra

AU - Oszurek, Oleg

AU - Bilic, Sanela

AU - Talhouk, Aline

AU - García-Closas, Montserrat

AU - Wang, Qin

AU - Tan, Adeline

AU - Farrell, Rhonda

AU - Kennedy, Catherine J.

AU - Jimenez-Linan, Mercedes

AU - Sundfeldt, Karin

AU - Etter, John L.

AU - Menkiszak, Janusz

AU - Goodman, Marc T.

AU - Klonowski, Paul

AU - Leung, Yee

AU - Winham, Stacey J.

AU - Moysich, Kirsten B.

AU - Behrens, Sabine

AU - deFazio, Anna

AU - Gorringe, Kylie L.

AU - Pharoah, Paul D. P.

AU - Stewart, Colin

AU - Cohen, Paul

AU - Ramus, Susan J.

AU - Köbel, Martin

PY - 2019/6/25

Y1 - 2019/6/25

N2 - 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.

AB - 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.

U2 - 10.1038/s41379-019-0302-0

DO - 10.1038/s41379-019-0302-0

M3 - Article

JO - Modern Pathology

JF - Modern Pathology

SN - 0893-3952

ER -