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CDX2 :
CDX2 : A Prognostic Marker in Metastatic Colorectal Cancer Defining a Better BRAF Mutated and a Worse KRAS Mutated Subgroup
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- Aasebo, Kristine (författare)
- Univ Bergen, Dept Clin Sci, Bergen, Norway
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- Dragomir, Anca (författare)
- Uppsala universitet,Klinisk och experimentell patologi,Department of Pathology, Uppsala University Hospital, Uppsala, Sweden
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- Sundström, Magnus (författare)
- Uppsala universitet,Klinisk och experimentell patologi,Department of Pathology, Uppsala University Hospital, Uppsala, Sweden
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- Mezheyeuski, Artur (författare)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Edqvist, Per-Henrik D (författare)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Eide, Geir Egil (författare)
- Univ Bergen, Dept Global Publ Hlth & Primary Care, Lifestyle Epidemiol Grp, Bergen, Norway;Haukeland Hosp, Clin Res Ctr, Bergen, Norway
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- Pontén, Fredrik (författare)
- Uppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab
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- Pfeiffer, Per (författare)
- Odense Univ Hosp, Dept Oncol, Odense, Denmark
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- Glimelius, Bengt (författare)
- Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab
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- Sorbye, Halfdan (författare)
- Univ Bergen, Dept Clin Sci, Bergen, Norway;Haukeland Hosp, Dept Oncol, Bergen, Norway
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(creator_code:org_t)
- 2020-02-11
- 2020
- Engelska.
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Ingår i: Frontiers in Oncology. - : FRONTIERS MEDIA SA. - 2234-943X. ; 10
- Relaterad länk:
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https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
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https://www.frontier...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Background: Survival of metastatic colorectal cancer (mCRC) patients has improved, but mainly for trial patients. New predictive and prognostic biomarkers validated in the general mCRC population are needed. Caudal-type homeobox 2 (CDX2) is an intestine-specific transcription factor with potential prognostic and predictive effect, but the importance in mCRC has not been fully investigated. Methods: Immunohistochemistry analysis of CDX2 was performed in a Scandinavian population-based cohort of mCRC (n = 796). Frequency, clinical and tumor characteristics, response rate, progression-free survival, and overall survival (OS) were estimated. Results: Loss of CDX2 expression was found in 87 (19%) of 452 stained cases, in 53% if BRAF mutated (BRAFmut) and in 9% if KRAS mutated (KRASmut). CDX2 loss was associated with microsatellite instability, BRAFmut, and poor differentiation and inversely associated with KRASmut. Patients with CDX2 loss received less first-line (53 vs. 64%, p = 0.050) and second-line (23 vs. 39%, p = 0.006) chemotherapy and secondary surgery (1 vs. 9%, p = 0.019). Median progression-free survival and OS for patients given first-line combination chemotherapy was 4 and 10 months if CDX2 loss vs. 9 and 24 months if CDX2 expressed (p = 0.001, p < 0.001). Immediate progression on first-line combination chemotherapy was seen in 35% of patients with CDX2 loss vs. 10% if CDX2 expressed (p = 0.003). Median OS in patients with BRAFmut or KRASmut and CDX2 expressed in tumor (both 21 months) was comparable to wild-type patients (27 months). However, if CDX2 loss, median OS was only 8 and 11 months in BRAFmut and KRASmut cases, respectively, and 10 months in double wild-type patients. In multivariate analysis, CDX2 loss (hazard ratio: 1.50, p = 0.027) and BRAFmut (hazard ratio: 1.62, p = 0.012) were independent poor prognostic markers for OS. Conclusion: In a population-based cohort of mCRC patients, CDX2 loss is an independent poor prognostic marker. Expression of CDX2 defines a new subgroup of BRAFmut cases with a much better prognosis. Loss of CDX2 defines a small group of KRASmut cases with a worse prognosis. Patients with CDX2 loss receive less palliative chemotherapy with less benefit and rarely reach secondary surgery.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- caudal type homeobox transcription factor
- CDX2
- colorectal cancer
- metastatic disease
- stage 4 colorectal cancer
- prognosis
- population based
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Aasebo, Kristine
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Dragomir, Anca
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Sundström, Magnu ...
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Mezheyeuski, Art ...
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Edqvist, Per-Hen ...
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Eide, Geir Egil
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Pontén, Fredrik
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Pfeiffer, Per
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Glimelius, Bengt
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Sorbye, Halfdan
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