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Metastatic colorectal carcinomas with high SATB2 expression are associated with better prognosis and response to chemotherapy: a population-based Scandinavian study.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. (Fredrik Pontén)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. (Johan Botling)
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2019 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, p. 1-7Article in journal (Refereed) Epub ahead of print
Abstract [en]

Background: Survival and response to therapy in patients with metastatic colorectal cancer (mCRC) are very heterogeneous. There is an unmet need for better markers of prognosis and treatment benefit for mCRC patients. The homeobox 2 gene SATB2 has a highly specific expression in colorectal tissue and is associated with better prognosis in non-metastatic CRC.Material and methods: A population-based cohort of 798 mCRC patients was analysed. From primary tumour material, protein expression was assessed by immunohistochemistry. BRAF and KRAS mutation status was also determined. Associations with clinicopathological data, overall and progression-free survival and response to first-line chemotherapy were analysed.Results: Tumour tissue and clinical data were available from 467 patients. SATB2 was strongly expressed in 58% of cases, significantly more in left-sided, low-grade and wild-type BRAF tumours. Patients with high SATB2 tumours had longer overall survival compared with low SATB2 tumours (median 13 vs 8 months respectively, p < .001). Chemotherapy was given to 282 patients (63%). Patients with high SATB2 tumours had longer OS (median 22 vs 15 months respectively, p = .001) and more often responded to chemotherapy than those with low SATB2 (objective response 43% vs 29%, p = .02; clinical response 83% vs 67%, p = .004). Progression-free survival on first-line irinotecan chemotherapy was longer in high SATB2 cases (median 8 vs 4 months respectively, p = .019). Patients with both low SATB2 expression and mutated BRAF (n = 69) had particularly poor survival compared to the rest (median 8 and 12 months respectively, p = .001). In multivariable analysis, the SATB2 findings were independent of known clinicopathological prognostic markers, including BRAF mutation status.Conclusion: Patients with mCRC expressing high level of SATB2 have better prognosis and response to chemotherapy than those with low SATB2 expression. Patients with both low SATB2 expression and mutated BRAF had particularly poor prognosis and could thus benefit from more aggressive therapies.

Place, publisher, year, edition, pages
2019. p. 1-7
National Category
Clinical Laboratory Medicine
Research subject
Pathology
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URN: urn:nbn:se:uu:diva-401723DOI: 10.1080/0284186X.2019.1691258PubMedID: 31769323OAI: oai:DiVA.org:uu-401723DiVA, id: diva2:1383785
Available from: 2020-01-08 Created: 2020-01-08 Last updated: 2020-01-08

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