Epithelial insulin receptor expression-prognostic relevance in colorectal cancer.

Autor:	Heckl SM; Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany., Pellinghaus M; Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany., Krüger S; Department of Pathology, Christian-Albrechts-University, Kiel, Germany., Bosselmann C; Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany., Wilhelm F; Department of Pathology, Christian-Albrechts-University, Kiel, Germany., Behrens HM; Department of Pathology, Christian-Albrechts-University, Kiel, Germany., Schreiber S; Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany., Röcken C; Department of Pathology, Christian-Albrechts-University, Kiel, Germany.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2018 Dec 25; Vol. 9 (101), pp. 37497-37508. Date of Electronic Publication: 2018 Dec 25 (Print Publication: 2018).
DOI:	10.18632/oncotarget.26490
Abstrakt:	Background: Metabolic reprogramming in cancer encompasses the insulin receptor (IR) as a player of energy homeostasis and proliferation. We aimed to characterize vascular (VIR) and epithelial (EIR) IR expression in CRC and correlate it with clinico-pathological parameters and survival. Methods: 1580 primary CRCs were explored by immunohistochemistry for evaluation of VIR and EIR. Subgroup analyses included in situ hybridization for IR isoform A (IR-A) and DNA mismatch repair protein immunohistochemistry. Clinico-pathological and survival parameters were studied. Results: High VIR was evident in 63.5% of all CRC samples and was associated with T-stage ( P = 0.005). EIR was present in 72.2% and was associated with lower T-stages ( P = 0.006) and UICC-stages ( P < 0.001). EIR negativity was associated with increased metastasis ( P = 0.028), nodal spread ( P < 0.001), lymphatic invasion ( P = 0.008) and a decreased tumor-specific ( P = 0.011) and overall survival ( P = 0.007; 95%-C.I.: 44.5-84.1). EIR negativity in UICC-stage II was associated with a significantly worse tumor-specific ( P = 0.045) and overall ( P = 0.043) survival. IR-A was expressed in CRC vessels and cells. Conclusions: We demonstrate VIR to be frequent in CRC and characterize EIR negativity as an important prognostic risk factor. The association between EIR negativity and worse survival in UICC-stage II should be prospectively evaluated for an application in therapeutic algorithms. Competing Interests: CONFLICTS OF INTEREST The authors declare no conflict of interest.
Databáze:	MEDLINE
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