Tumoral ANXA1 Is a Predictive Marker for Sunitinib Treatment of Renal Cancer Patients

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Niinivirta, MarjutUppsala universitet,Experimentell och klinisk onkologi,Uppsala University Hospital, Department of Oncology (author)

Tumoral ANXA1 Is a Predictive Marker for Sunitinib Treatment of Renal Cancer Patients

Article/chapterEnglish2017

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Ivyspring International Publisher,2017
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LIBRIS-ID:oai:DiVA.org:uu-339521
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-339521URI
https://doi.org/10.7150/jca.20889DOI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype

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Background and aims: There is no established predictive marker for the treatment of renal cancer. Metastatic renal cell carcinoma (mRCC) patients are often treated with sunitinib, a tyrosine kinase inhibitor. Sunitinibs anti-cancer effect is at least partly mediated through interfering with angiogenesis. Our aim with the current study was to assess annexin A1 (ANXA1), which stimulates angiogenesis, as a predictive marker for sunitinib therapy in mRCC patients. Since previous studies have indicated a predictive potential for cubilin, we also investigated the predictivity of ANXA1 combined with cubilin.Methods: ANXA1 expression was analysed in tumor tissue from a cohort of patients with advanced RCC (n= 139) using immunohistochemistry. Ninety-nine of the patients were treated with sunitinib in the first or second-line setting. Twenty-two of these were censored because of toxicity leading to the termination of treatment and the remaining (n= 77) were selected for the present study.Results: Twenty-five (32%) out of seventy-seven of the tumors lacked ANXA1 in the cytoplasm. On statistical analyses using Kaplan-Meier method, aNXA1 negative tumors were significantly associated with a longer treatment benefit in terms of progression free survival (PFS). Overall survival was also significantly better for patients with ANXA1 negative tumors. The combined ANXA1 positive and cubilin negative expression could more accurately than ANXA1 alone define the group not benefitting from treatment.Conclusions: Our results indicate that cytoplasmic expression of ANXA1 is a negative predictive marker for sunitinib therapy in mRCC patients. A possible explanation for this finding is that sunitinibs anti-angiogenic effect cannot overcome the pro-angiogenic drive from many ANXA1 proteins.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Klinisk laboratoriemedicin hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Clinical Laboratory Medicine hsv//eng
Renal cancer
sunitinib
tissue microarray
predictive marker
ANXA1
Patologi
Pathology

Added entries (persons, corporate bodies, meetings, titles ...)

Enblad, GunillaUppsala universitet,Experimentell och klinisk onkologi,Uppsala University Hospital, Department of Oncology(Swepub:uu)gunienbl (author)
Edqvist, Per-Henrik DUppsala universitet,Science for Life Laboratory, SciLifeLab,Experimentell och klinisk onkologi(Swepub:uu)peedq227 (author)
Pontén, FredrikUppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab,Fredrik Pontén(Swepub:uu)fredpont (author)
Dragomir, AncaUppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab,Fredrik Pontén(Swepub:uu)ancadrag (author)
Ullenhag, GustavUppsala universitet,Experimentell och klinisk onkologi,Uppsala University Hospital, Department of Oncology(Swepub:uu)gustulle (author)
Uppsala universitetExperimentell och klinisk onkologi (creator_code:org_t)

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In:Journal of Cancer: Ivyspring International Publisher8:19, s. 3975-39831837-9664

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By the author/editor: Niinivirta, Marj ...; Enblad, Gunilla; Edqvist, Per-Hen ...; Pontén, Fredrik; Dragomir, Anca; Ullenhag, Gustav

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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