Stains & CD markers
SOX17
Copyright: 2024, PathologyOutlines.com, Inc.
PubMed Search: SOX17
SOX17
Author: Pamela Wirth, Ph.D.
Editorial Board Member: Christian M. Schürch, M.D., Ph.D.
Deputy Editor-in-Chief: Gulisa Turashvili, M.D., Ph.D.
Last author update: 29 August 2024
Last staff update: 29 August 2024
Copyright: 2024, PathologyOutlines.com, Inc.
PubMed Search: SOX17
Table of Contents
Definition / general | Essential features | Terminology | Pathophysiology | Clinical features | Interpretation | Uses by pathologists | Prognostic factors | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative staining | Molecular / cytogenetics description | Sample pathology report | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Wirth P. SOX17. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsSOX17.html. Accessed December 25th, 2024.
Definition / general
- Member of SRY related high mobility group box transcription factor superfamily; plays a critical role in cardiovascular and hematopoietic development
- Part of F subgroup containing SOX7, SOX17 and SOX18
Essential features
- Epigenetically inactivated in many cancers; regulates proliferation, cell cycle and angiogenesis during cancer progression
- Involved in regulation of embryonic development and determination of cell fate
- Required for generation and maintenance of fetal hematopoietic stem cells
- Downregulation of SOX17 is associated with poor prognosis in advanced stages and higher grade tumors
Terminology
- SRY (sex determining region Y) box transcription factor 17
Pathophysiology
- SOX17 encodes a transcription factor involved in Wnt / beta catenin and Notch signaling pathways during development (Genome Med 2018;10:56)
- Negatively regulates beta catenin / T cell transcription factor pathways, thereby suppressing tumor growth
- Associated with tumorigenic processes such as sustained cellular proliferation in absence of growth signals (Oncotarget 2016;7:76036)
- May act as a tumor suppressor in some cancers and oncogenic in others
- SOX17 may be highly expressed in normal cervical tissue, moderately expressed in high grade squamous intraepithelial lesions and minimally expressed in cervical carcinomas (Cell Death Dis 2018;9:741)
- SOX17 gene is downregulated by methylation during malignant progression of gastrointestinal carcinomas (Gastroenterology 2009;137:1346)
- Early stage colorectal adenomas and cancers upregulate SOX17 to escape immune surveillance (Nature 2024;627:636)
Clinical features
- Higher SOX17 protein expression is associated with chemosensitivity in endometrial cancer tissues (cisplatin) (Cancer Cell Int 2016;16:29)
Interpretation
- Nuclear expression
Uses by pathologists
- Sensitive (100%) and specific (98.2%) for differential diagnosis of metastatic gynecologic neoplasms (Cancer Cytopathol 2023;131:465)
- Identification of Müllerian high grade serous carcinoma that has metastasized to breast and axilla, which can sometimes be misdiagnosed as primary breast carcinoma
- Useful for diagnoses involving thyroid or kidney tumors as sites of origin (SOX17 would be negative in these tumors) (Mod Pathol 2023;36:100038)
- Useful for differentiating breast carcinomas (negative for SOX17) from ovarian carcinomas (positive for SOX17) (Mod Pathol 2023;36:100038)
Prognostic factors
- Patients with endometrial carcinomas expressing higher SOX17 levels had longer recurrence free survival (Oncotarget 2016;7:76036)
- Downregulation of SOX17 is associated with poor prognosis in advanced stages and higher grade tumors (Semin Cancer Biol 2020;67:65)
Microscopic (histologic) images
Contributed by Pamela Wirth, Ph.D. (source: Human Protein Atlas)
Endometrial adenocarcinoma
Ovarian
cystadenocarcinoma
Cervical squamous cell carcinoma
Testis carcinoma
Stomach adenocarcinoma
Head and neck carcinoma
Positive staining - normal
- Positive nuclear expression in normal reproductive tissues (endometrial glands, endocervical glands, fallopian tube epithelium, germ cell precursors of spermatocytes) (Oncotarget 2016;7:76036)
- Expressed in vascular endothelial cells; serves as an internal control (Mod Pathol 2023;36:100038)
Positive staining - disease
- Expressed in angiosarcomas (100%) (Mod Pathol 2023;36:100038)
- Highly expressed in the following ovarian tumors
- Serous carcinoma (91%)
- Clear cell carcinoma (91%)
- Endometrioid carcinoma (89%)
- Germ cell tumors (75%)
- Yolk sac tumors (100%)
Negative staining
- Mostly negative in the following tissues (Mod Pathol 2023;36:100038)
- Mucinous carcinomas
- Sex cord stromal tumors
- Squamous cell carcinomas of the cervix
- Renal clear cell carcinoma, chromophobe renal cell carcinoma and renal papillary cell carcinoma are negative for nuclear expression of SOX17 (Cancer Genomics Proteomics;20:433)
- Thyroid tumors including papillary, follicular and anaplastic are negative for nuclear expression of SOX17 (Cancer Genomics Proteomics;20:433)
- Invasive ductal and lobular breast carcinoma (Cancer Genomics Proteomics;20:433)
- Colon adenocarcinoma (Cancer Genomics Proteomics;20:433)
- Meningioma, astrocytoma, oligodendroglioma, glioblastoma
- Pancreatic ductal carcinoma
- Adrenocortical adenoma and carcinoma
- Lung adenocarcinoma and lung squamous cell carcinoma (Cancer Genomics Proteomics;20:433)
Molecular / cytogenetics description
- Somatic SOX17 mutations identified in endometrial endometrioid carcinoma (EEC) include
- 2 recurrent hotspot missense mutations
- Frameshift mutations
- Stop mutations (most common in EECs)
- SOX17 can be epigenetically silenced through promoter methylation (Oncotarget 2017;8:68758)
Sample pathology report
- Right ovary and fallopian tube, salpingo-oophorectomy:
- Ovary, clear cell carcinoma (see comment)
- Fallopian tube: Unremarkable
- Comment: Note is made of the clinical history of abdominal distension, endometriosis and a solid cystic adnexal mass on imaging. Microscopically, the right ovarian tumor reveals papillary and tubulocystic architecture with pale eosinophilic to clear cells and moderately pleomorphic nuclei. Immunohistochemical stains show the tumor to be positive for napsin A, HNF1β, CK7 and SOX17; and negative for ER, PR and CK20. The findings are consistent with clear cell carcinoma.
Board review style question #1
Which statement correctly describes the expression and clinical significance of SOX17 in different tissues?
- Downregulation of SOX17 is associated with better prognosis in advanced stages of cancer
- Higher SOX17 expression in endometrial cancer is associated with chemosensitivity to cisplatin
- SOX17 expression is typically high in kidney tumors and lung tumors
- SOX17 is highly expressed in mucinous carcinomas and thyroid tumors
Board review style answer #1
B. Higher SOX17 expression in endometrial cancer is associated with chemosensitivity to cisplatin. SOX17 overexpression is correlated with decreased tumor growth and increased sensitivity to cisplatin by upregulation of apoptotic pathways. Answer A is incorrect because SOX17 downregulation is associated with advanced stage tumors and poorer outcomes in patients with low expression levels. Answers C and D are incorrect because SOX17 expression is generally low to negative in kidney tumors, lung tumors, mucinous carcinomas and thyroid tumors.
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Reference: SOX17
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Board review style question #2
Which of the following tissues would most likely show negative SOX17 staining?
- Angiosarcoma
- Endometrial glands
- Squamous cell carcinoma of the cervix
- Vascular endothelial cells
Board review style answer #2
C. Squamous cell carcinoma of the cervix. SOX17 expression in cervical cancer is low (or absent) compared with normal cervix and high grade squamous intraepithelial lesions. Answer D is incorrect because SOX17 is typically expressed in vascular endothelial cells, which can be used as an internal control. Answers A and B are incorrect because SOX17 expression is typically high in angiosarcoma and endometrial glands.
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Reference: SOX17
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