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Mod Pathol. 2019 Dec;32(12):1834-1846. doi: 10.1038/s41379-019-0302-0. Epub 2019 Jun 25.

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.

Author information

1
School of Women's and Children's Health, Faculty of Medicine, University of NSW Sydney, Sydney, NSW, Australia.
2
Prince of Wales Clinical School. UNSW Sydney, Sydney, NSW, Australia.
3
Adult Cancer Program. Lowy Cancer Research Centre, Sydney, Australia.
4
Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, AB, Canada.
5
Pathology Department, Catholic University of Health and Allied Sciences-Bugando, Mwanza, Tanzania.
6
British Columbia's Ovarian Cancer Research (OVCARE) Program, Vancouver General Hospital, BC Cancer Agency and University of British Columbia, Vancouver, BC, Canada.
7
Department of Molecular Oncology, BC Cancer Agency Research Centre, Vancouver, BC, Canada.
8
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
9
Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
10
Department of Histopathology, Imperial College London, Hammersmith Hospital, London, UK.
11
University of Texas MD Anderson Cancer Center, Houston, TX, USA.
12
Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
13
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology. Royal Alexandra Hospital, Edmonton, AB, Canada.
14
Tissue Bank of the National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
15
Department of Pathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
16
Bendat Family Comprehensive Cancer Centre, St John of God Subiaco Hospital, Subiaco, Western Australia, Australia.
17
NSW Health Pathology. Prince of Wales Hospital, Sydney, NSW, Australia.
18
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
19
Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.
20
Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
21
Department of Health Science Research, Division of Biomedical Statistics and Informatics. Mayo Clinic, Rochester, MN, USA.
22
Department of Health Science Research, Division of Epidemiology. Mayo Clinic, Rochester, MN, USA.
23
MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, University College London, London, UK.
24
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
25
Division of Cancer Epidemiology and Genetics. National Cancer Institute, Bethesda, MD, USA.
26
Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
27
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
28
Division of Obstetrics and Gynaecology, Faculty of Health and Medical Sciences, University of Western Australia, Crawley, Western Australia, Australia.
29
Western Women's Pathology, Western Diagnostic Pathology, Wembley, Western Australia, Australia.
30
Prince of Wales Private Hospital, Randwick, NSW, Australia.
31
Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
32
Department of Gynaecological Oncology, Westmead Hospital, Sydney, NSW, Australia.
33
Department of Histopathology. Addenbrookes Hospital, Cambridge, UK.
34
Department of Obstetrics and Gynecology, Sahlgrenska Cancer Center, Inst Clinical Scienses, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
35
Department of Gynecology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
36
Division of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
37
Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, Szczecin, Poland.
38
Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
39
Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
40
Histopathology Department, King Edward Memorial Hospital, Perth, Western Australia, Australia.
41
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
42
Department of Obstetrics and Gynecology, Fryderyk Chopin University Hospital No 1, Faculty of Medicine, Rzeszów University, Rzeszów, Poland.
43
Ovarian Cancer Center of Excellence, Womens Cancer Research Program, Magee-Womens Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
44
Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
45
Womens Cancer Research Center, Magee-Womens Research Institute and Hillman Cancer Center, Pittsburgh, PA, USA.
46
University of Hawaii Cancer Center, Honolulu, HI, USA.
47
Genetic Pathology Evaluation Centre, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada.
48
Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
49
Department of Laboratory Medicine and Pathology, Division of Anatomic Pathology. Mayo Clinic, Rochester, MN, USA.
50
Department of Obstetrics and Gynecology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
51
St George Private Hospital, Kogarah, NSW, Australia.
52
Pathology West ICPMR Westmead, Westmead Hospital, The University of Sydney, Sydney, NSW, Australia.
53
University of Western Sydney at Westmead Hospital, Westmead, NSW, Australia.
54
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
55
Center for Cancer Prevention and Translational Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
56
Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
57
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
58
Gynaecological Cancer Research Centre, Women's Cancer, Institute for Women's Health, University College London, London, UK.
59
Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.
60
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
61
Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH). University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
62
Alberta Health Services-Cancer Care, Calgary, AB, Canada.
63
University of New Mexico Health Sciences Center. University of New Mexico, Albuquerque, NM, USA.
64
Department of Cancer Epidemiology and Prevention Research, Alberta Health Services, Calgary, AB, Canada.
65
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
66
Division of Breast Cancer Research. Institute of Cancer Research, London, UK.
67
Division of Bioscience, Brunel University, London, UK.
68
Department of Pathology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
69
The Crown Princess Mary Cancer Centre Westmead, Sydney-West Cancer Network. Westmead Hospital, Sydney, NSW, Australia.
70
Departments of Surgery and Oncology, Tom Baker Cancer Centre, Calgary, AB, Canada.
71
The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW, Australia.
72
Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, AB, Canada. Martin.Koebel@albertapubliclabs.ca.

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.

PMID:
31239549
DOI:
10.1038/s41379-019-0302-0

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