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-Grabarek; Oleg 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

doi:10.1038/s41379-019-0302-0

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-Grabarek

Oleg 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

Department of Epidemiology and Environmental Health

University of New South Wales
Adult Cancer Program. Lowy Cancer Research Centre
University of Calgary
Catholic University of Health and Allied Sciences
University of British Columbia
Provincial Health Services Authority
University of Hawai'i at Mānoa
Imperial College Healthcare NHS Trust
University of Texas MD Anderson Cancer Center
Roswell Park Cancer Institute
Royal Alexandra Hospital, Edmonton
Heidelberg University
St John of God Subiaco Hospital
Prince of Wales Hospital
The Institute of Cancer Research
Pomeranian Medical University in Szczecin
Mayo Clinic Rochester, MN
University College London
National Institutes of Health
University of Cambridge
University of Western Australia
Western Diagnostic Pathology
Prince of Wales Private Hospital
The University of Sydney
Westmead Hospital
Cambridge University Hospitals NHS Foundation Trust
University of Gothenburg
Sahlgrenska University Hospital
Cedars-Sinai Medical Center
King Edward Memorial Hospital for Women
German Cancer Research Center
University of Rzeszów
University of Pittsburgh
Medical University of South Carolina
St George Private Hospital
Western Sydney University
University of Southern California
Peter Maccallum Cancer Centre
University of Melbourne
University of Hamburg
Alberta Health Services
University of New Mexico
Brunel University London
Tom Baker Cancer Centre
Garvan Institute of Medical Research

Research output: Contribution to journal › Article › peer-review

76 Scopus citations

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 language	English
Pages (from-to)	1834-1846
Number of pages	13
Journal	Modern Pathology
Volume	32
Issue number	12
DOIs	https://doi.org/10.1038/s41379-019-0302-0
State	Published - Dec 1 2019

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10.1038/s41379-019-0302-0

Cite this

Meagher, N. S., Wang, L., Rambau, P. F., Intermaggio, M. P., Huntsman, D. G., Wilkens, L. R., El-Bahrawy, M. A., Ness, R. B., Odunsi, K., Steed, H., Herpel, E., Anglesio, M. S., Zhang, B., Lambie, N., Swerdlow, A. J., Lubiński, J., Vierkant, R. A., Goode, E. L., Menon, U., ... 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, 32(12), 1834-1846. https://doi.org/10.1038/s41379-019-0302-0

@article{39234e7a5a8f4ae2995c692f7b9bc3df,

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 = "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 Lubi{\'n}ski 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 Tomasz Kluz and Edwards, \{Robert P.\} and Jacek Gronwald and Francesmary Modugno and Hernandez, \{Brenda Y.\} and Christine Chow and Kelemen, \{Linda E.\} and Keeney, \{Gary L.\} and Carney, \{Michael E.\} and Yanina Natanzon and Gregory Robertson and Raghwa Sharma and Gayther, \{Simon A.\} and Jennifer Alsop and Hugh Luk and Chloe Karpinskyj and Ian Campbell and Peter Sinn and Aleksandra Gentry-Maharaj and Penny Coulson and Jenny Chang-Claude and Mitul Shah and Martin Widschwendter and Katrina Tang and Schoemaker, \{Minouk J.\} and Koziak, \{Jennifer M.\} and Cook, \{Linda S.\} and Brenton, \{James D.\} and Frances Daley and Bj{\"o}rg Kristjansdottir and Constantina Mateoiu and Larson, \{Melissa C.\} and Harnett, \{Paul R.\} and Audrey Jung and Anna deFazio and Gorringe, \{Kylie L.\} and Pharoah, \{Paul D.P.\} and Parham Minoo and Colin Stewart and Bathe, \{Oliver F.\} and Xianyong Gui and Paul Cohen and Ramus, \{Susan J.\} and Martin K{\"o}bel",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licensc to United States \& Canadian Academy of Pathology.",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41379-019-0302-0",

language = "English",

volume = "32",

pages = "1834--1846",

journal = "Modern Pathology",

issn = "0893-3952",

publisher = "Elsevier B.V.",

number = "12",

}

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, vol. 32, no. 12, pp. 1834-1846. https://doi.org/10.1038/s41379-019-0302-0

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. et al.
In: Modern Pathology, Vol. 32, No. 12, 01.12.2019, p. 1834-1846.

Research output: Contribution to journal › Article › peer-review

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 - 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 - 2019/12/1

Y1 - 2019/12/1

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.

UR - https://www.scopus.com/pages/publications/85068207514

U2 - 10.1038/s41379-019-0302-0

DO - 10.1038/s41379-019-0302-0

M3 - Article

C2 - 31239549

AN - SCOPUS:85068207514

SN - 0893-3952

VL - 32

SP - 1834

EP - 1846

JO - Modern Pathology

JF - Modern Pathology

IS - 12

ER -

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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