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Prognostic value of c-FLIPL/s, HIF-1α, and NF-κβ in stage II and III rectal cancer

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Abstract

Locally advanced rectal cancer (LARC) is associated with a 25 % rate of metastases. The prognostic and predictive relevances of the expression of five proteins (c-FLIPL/s, HIF-1α, β-catenin, p65, and p105/p50 NF-κβ) were assessed. This is a retrospective study. From 1998 to 2009, 152 patients with stage II/III rectal cancer were treated with radio-chemotherapy. TMAs constructed with tumor and normal tissue from the diagnostic endoscopic biopsy and the surgical specimen after chemoradiotherapy were subjected to immunohistochemical (IHC) analysis. Results were correlated with clinical and pathological data, including progression-free survival (PFS). Four different IHC conditions were independent prognostic parameters for PFS: (1) cytoplasmic c-FLIPL/s (p = 0.007), (2) nuclear HIF-1α (p = 0.020), (3) a change in the cytoplasmic p65 between the diagnostic biopsy and the post-treatment specimen (p = 0.004), and (4) a change in the cytoplasmic c-FLIPL/s between the diagnostic biopsy and the post-treatment specimen (p = 0.021). Three different protein expression profiles, combining biomarkers, showed prognostic significance. IHC evaluation of these biomarkers in our three protein expression profiles may help to identify patients with worse prognosis and design more effective therapeutic strategies to personalize the treatment of rectal cancer.

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Acknowledgements

The authors thank Dr. F. Badia and Dr. R. Oncins and the members of the Colorectal Cancer Tumor Boards in Lleida for providing the pathological material and follow-up data. Work supported by the Xarxa de Bancs de Tumors de Catalunya sponsored by Pla Director d’Oncología de Catalunya (XBTC) and IRBLleida Biobank (B.0000682) and Plataforma Biobancos PT13/0010/0014.

Funding sources for this work

This work was supported by grants 2009SGR794, RD12/0036/0013.

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No financial disclosures.

Conflict of interest statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Departments of Pathology and Medical Oncology, Hospital Universitari Arnau de Vilanova. Universitat de Lleida, IRBLleida, Av. Rovira Roure, 80, 25198, Lleida, Spain

    Anna Novell, Jordi Tarragona, Antonieta Salud & Xavier Matias-Guiu

  2. Department of Biostatistics & Methological Support, IRBLleida, Lleida, Spain

    Montserrat Martínez-Alonso

  3. Department of Radiation Oncology, Hospital Universitari Arnau de Vilanova. Universitat de Lleida, IRBLleida, Lleida, Spain

    Moises Mira

  4. Department of Medical Oncology, Hospital Universitari Arnau de Vilanova. Universitat de Lleida, IRBLleida, Lleida, Spain

    Antonieta Salud

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  1. Anna Novell
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  2. Montserrat Martínez-Alonso
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Correspondence to Antonieta Salud or Xavier Matias-Guiu.

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Antonieta Salud and Xavier Matias-Guiu are both senior co-authors.

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Novell, A., Martínez-Alonso, M., Mira, M. et al. Prognostic value of c-FLIPL/s, HIF-1α, and NF-κβ in stage II and III rectal cancer. Virchows Arch 464, 645–654 (2014). https://doi.org/10.1007/s00428-014-1572-z

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  • DOI: https://doi.org/10.1007/s00428-014-1572-z

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