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SATB2 in Combination With Cytokeratin 20 Identifies Over 95% of all Colorectal Carcinomas
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
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2011 (English)In: American Journal of Surgical Pathology, ISSN 0147-5185, E-ISSN 1532-0979, Vol. 35, no 7, 937-948 p.Article in journal (Refereed) Published
Abstract [en]

The special AT-rich sequence-binding protein 2 (SATB2), a nuclear matrix-associated transcription factor and epigenetic regulator, was identified as a tissue type-specific protein when screening protein expression patterns in human normal and cancer tissues using an antibody-based proteomics approach. In this respect, the SATB2 protein shows a selective pattern of expression and, within cells of epithelial lineages, SATB2 expression is restricted to glandular cells lining the lower gastrointestinal tract. The expression of SATB2 protein is primarily preserved in cancer cells of colorectal origin, indicating that SATB2 could function as a clinically useful diagnostic marker to distinguish colorectal cancer (CRC) from other types of cancer. The aim of this study was to further explore and validate the specific expression pattern of SATB2 as a clinical biomarker and to compare SATB2 with the well-known cytokeratin 20 (CK20). Immunohistochemistry was used to analyze the extent of SATB2 expression in tissue microarrays with tumors from 9 independent cohorts of patients with primary and metastatic CRCs (n = 1882). Our results show that SATB2 is a sensitive and highly specific marker for CRC with distinct positivity in 85% of all CRCs, and that SATB2 and/or CK20 was positive in 97% of CRCs. In conclusion, the specific expression of SATB2 in a large majority of CRCs suggests that SATB2 can be used as an important complementary tool for the differential diagnosis of carcinoma of unknown primary origin.

Place, publisher, year, edition, pages
2011. Vol. 35, no 7, 937-948 p.
Keyword [en]
SATB2, colorectal cancer, antibody-based proteomics, diagnostic biomarker
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-156012DOI: 10.1097/PAS.0b013e31821c3daeISI: 000291676200001OAI: oai:DiVA.org:uu-156012DiVA: diva2:429781
Available from: 2011-07-05 Created: 2011-07-05 Last updated: 2016-01-13Bibliographically approved
In thesis
1. Protein Expression Profiling of Cancer Biomarkers
Open this publication in new window or tab >>Protein Expression Profiling of Cancer Biomarkers
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The Human Protein Atlas project is a Swedish research initiative that uses antibody-based proteomics for large scale protein profiling in human tissues and cells. Affinity-purified antibodies are produced within the project and used for immunohistochemical staining on tissue micro arrays (TMAs) in order to map the human proteome and publish the result in a protein atlas (www.proteinatlas.org). In this thesis, TMAs were used for analysis of protein expression patterns in order to identify and explore potential biomarkers of clinical relevance.

In Paper I, protein expression of SATB2 was studied in colorectal cancer. The results show that SATB2 is a sensitive and specific biomarker for colorectal cancer, staining 85% of all investigated tumors. Moreover, SATB2 in combination with CK20 showed positivity in 97% of all colorectal carcinomas and is therefore suitable as a complementary tool in clinical differential diagnostics of cancer.

In Paper II, ANLN was explored as a prognostic biomarker for breast cancer. A high nuclear fraction of ANLN in breast cancer was significantly correlated to large tumor size, high histological grade, hormone receptor negative tumors, high proliferation rate and poor prognosis. Furthermore, ANLN depletion in breast cancer cell lines resulted in cell cycle arrest and cellular senescence with altered cell morphology.

In Paper III, young age at breast cancer diagnosis was investigated as an independent risk factor for poor prognosis. TMAs were produced from a selection of patients from a previously defined register-based cohort. The analysis shows that young women with luminal B tumors have a 2.2-fold higher risk of dying of breast cancer compared to older women.

In Paper IV, vascular expression of CD93 was explored by image analysis of the tissue-based breast cancer cohort produced in Paper III. The analysis shows that young women with breast cancer display a significantly higher CD93-positive vessel area in their tumors. High CD93-positive vessel area was significantly associated with hormone receptor negative tumors, grade, Ki-67, EGFR and a poor prognosis.

In conclusion, this thesis shows that protein expression profiling using TMAs is an important tool for identifying and exploring potential novel biomarkers for cancer.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 53 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1161
Antibody-based proteomics, Biomarker, SATB2, Colorectal cancer, ANLN, Breast cancer, CD93, Angiogenesis
National Category
Basic Medicine
Research subject
urn:nbn:se:uu:diva-265513 (URN)978-91-554-9404-9 (ISBN)
Public defence
2015-12-18, Rudbeck hall, Rudbeck laboratory, Dag Hammarskjölds väg 20, Uppsala, 13:15 (English)
Knut and Alice Wallenberg Foundation
Available from: 2015-11-27 Created: 2015-10-30 Last updated: 2016-01-13

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Molecular and Morphological PathologyBiomedical Radiation SciencesDepartment of Surgical SciencesDepartment of Genetics and PathologyColorectal SurgeryOncology
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American Journal of Surgical Pathology
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