RESUMEN
BACKGROUND: The insulin-like growth factor 1 receptor (IGF1R) is suspected to be involved in colorectal carcinogenesis and has been associated with worse survival in colorectal cancer (CRC). We hypothesized that the alleged suspect might be in truth beyond any suspicion. We investigated if the expression of the IGF1R in CRC correlates with (1) clinicopathological patient characteristics, including survival, and hence is involved in colon cancer biology; (2) the expression of the IGF1R in CRC is linked to the expression of the insulin receptor (IR). METHODS: We evaluated 4497 CRC samples from 1499 patients for the expression of IGF1R in tumor cells by immunohistochemistry. Cytoplasmic (cCC-IGF1R) and membranous (mCC-IGF1R) immunostaining was evaluated by employing a modified HistoScore (HScore), which was dichotomized into low or high IGF1R expressions. The IGF1R status was correlated with clinicopathological patient characteristics, survival and the IR expression status. RESULTS: cCC-IGF1R and mCC-IGF1R (HScore> 0) were found in 85.4 and 60.8% of all CRCs. After dichotomization of the HScores, 54.9 and 48.6% were classified as cCC-IGF1R-high and mCC-IGF1R-high, respectively. IGF1R was associated with tumor localization, local tumor growth, lymphatic vessel invasion, grading, mismatch repair protein expression status and IR-expression. We found no significant association with overall or tumor-specific survival, with a tendency for an even improved overall survival for cCC-IGF1R. CONCLUSIONS: IGF1R expression is frequent and biologically relevant in CRC, but does not correlate with patient survival. The IGF1R might be beyond suspicion in CRC after all.
Asunto(s)
Neoplasias del Colon/metabolismo , Neoplasias Colorrectales/metabolismo , Proteínas de Neoplasias/metabolismo , Receptor IGF Tipo 1/metabolismo , Receptor de Insulina/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Colon/mortalidad , Neoplasias Colorrectales/mortalidad , Citoplasma/química , Reparación del ADN , Femenino , Genes ras/genética , Técnicas de Genotipaje , Humanos , Inmunohistoquímica , Masculino , Proteínas de la Membrana/análisis , Persona de Mediana Edad , Proteínas de Neoplasias/análisis , Pronóstico , Receptor IGF Tipo 1/análisis , Receptor de Insulina/análisis , Análisis de Supervivencia , Análisis de Matrices TisularesRESUMEN
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.
