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

Nicola S. Meagher, Linyuan Wang, Peter F. Rambau, Maria P. Intermaggio, David G. Huntsman, Lynne R. Wilkens, Mona A. El-Bahrawy, Roberta B. Ness, Kunle Odunsi, Helen Steed, Esther Herpel, Michael S. Anglesio, Bonnie Zhang, Neil Lambie, Anthony J. Swerdlow, Jan Lubiński, Robert A. Vierkant, Ellen L. Goode, Usha Menon, Aleksandra Toloczko-GrabarekOleg Oszurek, Sanela Bilic, Aline Talhouk, Montserrat García-Closas, Qin Wang, Adeline Tan, Rhonda Farrell, Catherine J. Kennedy, Mercedes Jimenez-Linan, Karin Sundfeldt, John L. Etter, Janusz Menkiszak, Marc T. Goodman, Paul Klonowski, Yee Leung, Stacey J. Winham, Kirsten B. Moysich, Sabine Behrens, Tomasz Kluz, Robert P. Edwards, Jacek Gronwald, Francesmary Modugno, Brenda Y. Hernandez, Christine Chow, Linda E. Kelemen, Gary L. Keeney, Michael E. Carney, Yanina Natanzon, Gregory Robertson, Raghwa Sharma, Simon A. Gayther, Jennifer Alsop, Hugh Luk, Chloe Karpinskyj, Ian Campbell, Peter Sinn, Aleksandra Gentry-Maharaj, Penny Coulson, Jenny Chang-Claude, Mitul Shah, Martin Widschwendter, Katrina Tang, Minouk J. Schoemaker, Jennifer M. Koziak, Linda S. Cook, James D. Brenton, Frances Daley, Björg Kristjansdottir, Constantina Mateoiu, Melissa C. Larson, Paul R. Harnett, Audrey Jung, Anna deFazio, Kylie L. Gorringe, Paul D.P. Pharoah, Parham Minoo, Colin Stewart, Oliver F. Bathe, Xianyong Gui, Paul Cohen, Susan J. Ramus, Martin Köbel

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 (US)
JournalModern Pathology
DOIs
StateAccepted/In press - Jan 1 2019

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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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. / Meagher, Nicola S.; Wang, Linyuan; Rambau, Peter F.; Intermaggio, Maria P.; Huntsman, David G.; Wilkens, Lynne R.; El-Bahrawy, Mona A.; Ness, Roberta B.; Odunsi, Kunle; Steed, Helen; Herpel, Esther; Anglesio, Michael S.; Zhang, Bonnie; Lambie, Neil; Swerdlow, Anthony J.; Lubiński, Jan; Vierkant, Robert A.; Goode, Ellen L.; Menon, Usha; Toloczko-Grabarek, Aleksandra; Oszurek, Oleg; Bilic, Sanela; Talhouk, Aline; García-Closas, Montserrat; Wang, Qin; Tan, Adeline; Farrell, Rhonda; Kennedy, Catherine J.; Jimenez-Linan, Mercedes; Sundfeldt, Karin; Etter, John L.; Menkiszak, Janusz; Goodman, Marc T.; Klonowski, Paul; Leung, Yee; Winham, Stacey J.; Moysich, Kirsten B.; Behrens, Sabine; Kluz, Tomasz; Edwards, Robert P.; Gronwald, Jacek; Modugno, Francesmary; Hernandez, Brenda Y.; Chow, Christine; Kelemen, Linda E.; Keeney, Gary L.; Carney, Michael E.; Natanzon, Yanina; Robertson, Gregory; Sharma, Raghwa; Gayther, Simon A.; Alsop, Jennifer; Luk, Hugh; Karpinskyj, Chloe; Campbell, Ian; Sinn, Peter; Gentry-Maharaj, Aleksandra; Coulson, Penny; Chang-Claude, Jenny; Shah, Mitul; Widschwendter, Martin; Tang, Katrina; Schoemaker, Minouk J.; Koziak, Jennifer M.; Cook, Linda S.; Brenton, James D.; Daley, Frances; Kristjansdottir, Björg; Mateoiu, Constantina; Larson, Melissa C.; Harnett, Paul R.; Jung, Audrey; deFazio, Anna; Gorringe, Kylie L.; Pharoah, Paul D.P.; Minoo, Parham; Stewart, Colin; Bathe, Oliver F.; Gui, Xianyong; Cohen, Paul; Ramus, Susan J.; Köbel, Martin.

In: Modern Pathology, 01.01.2019.

Research output: Contribution to journalArticle

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, Lubiński, J, Vierkant, RA, Goode, EL, Menon, U, Toloczko-Grabarek, A, Oszurek, O, Bilic, S, Talhouk, A, García-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 & Köbel, M 2019, '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', Modern Pathology. https://doi.org/10.1038/s41379-019-0302-0
Meagher, Nicola S. ; Wang, Linyuan ; Rambau, Peter F. ; Intermaggio, Maria P. ; Huntsman, David G. ; Wilkens, Lynne R. ; El-Bahrawy, Mona A. ; Ness, Roberta B. ; Odunsi, Kunle ; Steed, Helen ; Herpel, Esther ; Anglesio, Michael S. ; Zhang, Bonnie ; Lambie, Neil ; Swerdlow, Anthony J. ; Lubiński, Jan ; Vierkant, Robert A. ; Goode, Ellen L. ; Menon, Usha ; Toloczko-Grabarek, Aleksandra ; Oszurek, Oleg ; Bilic, Sanela ; Talhouk, Aline ; García-Closas, Montserrat ; Wang, Qin ; Tan, Adeline ; Farrell, Rhonda ; Kennedy, Catherine J. ; Jimenez-Linan, Mercedes ; Sundfeldt, Karin ; Etter, John L. ; Menkiszak, Janusz ; Goodman, Marc T. ; Klonowski, Paul ; Leung, Yee ; Winham, Stacey J. ; Moysich, Kirsten B. ; Behrens, Sabine ; Kluz, Tomasz ; Edwards, Robert P. ; Gronwald, Jacek ; Modugno, Francesmary ; Hernandez, Brenda Y. ; Chow, Christine ; Kelemen, Linda E. ; Keeney, Gary L. ; Carney, Michael E. ; Natanzon, Yanina ; Robertson, Gregory ; Sharma, Raghwa ; Gayther, Simon A. ; Alsop, Jennifer ; Luk, Hugh ; Karpinskyj, Chloe ; Campbell, Ian ; Sinn, Peter ; Gentry-Maharaj, Aleksandra ; Coulson, Penny ; Chang-Claude, Jenny ; Shah, Mitul ; Widschwendter, Martin ; Tang, Katrina ; Schoemaker, Minouk J. ; Koziak, Jennifer M. ; Cook, Linda S. ; Brenton, James D. ; Daley, Frances ; Kristjansdottir, Björg ; Mateoiu, Constantina ; Larson, Melissa C. ; Harnett, Paul R. ; Jung, Audrey ; deFazio, Anna ; Gorringe, Kylie L. ; Pharoah, Paul D.P. ; Minoo, Parham ; Stewart, Colin ; Bathe, Oliver F. ; Gui, Xianyong ; Cohen, Paul ; Ramus, Susan J. ; Köbel, Martin. / 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. In: Modern Pathology. 2019.
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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",
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.",
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day = "1",
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journal = "Modern Pathology",
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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 - 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 - Kluz, Tomasz

AU - Edwards, Robert P.

AU - Gronwald, Jacek

AU - Modugno, Francesmary

AU - Hernandez, Brenda Y.

AU - Chow, Christine

AU - Kelemen, Linda E.

AU - Keeney, Gary L.

AU - Carney, Michael E.

AU - Natanzon, Yanina

AU - Robertson, Gregory

AU - Sharma, Raghwa

AU - Gayther, Simon A.

AU - Alsop, Jennifer

AU - Luk, Hugh

AU - Karpinskyj, Chloe

AU - Campbell, Ian

AU - Sinn, Peter

AU - Gentry-Maharaj, Aleksandra

AU - Coulson, Penny

AU - Chang-Claude, Jenny

AU - Shah, Mitul

AU - Widschwendter, Martin

AU - Tang, Katrina

AU - Schoemaker, Minouk J.

AU - Koziak, Jennifer M.

AU - Cook, Linda S.

AU - Brenton, James D.

AU - Daley, Frances

AU - Kristjansdottir, Björg

AU - Mateoiu, Constantina

AU - Larson, Melissa C.

AU - Harnett, Paul R.

AU - Jung, Audrey

AU - deFazio, Anna

AU - Gorringe, Kylie L.

AU - Pharoah, Paul D.P.

AU - Minoo, Parham

AU - Stewart, Colin

AU - Bathe, Oliver F.

AU - Gui, Xianyong

AU - Cohen, Paul

AU - Ramus, Susan J.

AU - Köbel, Martin

PY - 2019/1/1

Y1 - 2019/1/1

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.

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DO - 10.1038/s41379-019-0302-0

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