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Epithelial insulin receptor expression-prognostic relevance in colorectal cancer.


ABSTRACT: 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.

SUBMITTER: Heckl SM 

PROVIDER: S-EPMC6331016 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Epithelial insulin receptor expression-prognostic relevance in colorectal cancer.

Heckl Steffen M SM   Pellinghaus Marie M   Krüger Sandra S   Bosselmann Clara C   Wilhelm Franziska F   Behrens Hans-Michael HM   Schreiber Stefan S   Röcken Christoph C  

Oncotarget 20181225 101


<h4>Background</h4>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.<h4>Methods</h4>1580 primary CRCs were explored by immunohistochemistry for evaluation of VIR and EIR. Subgroup analyses included <i>in situ</i> hybridization for IR isoform A (IR-A) and DNA mismatch repair  ...[more]

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