Heckl Steffen M, Pellinghaus Marie, Krüger Sandra, Bosselmann Clara, Wilhelm Franziska, Behrens Hans-Michael, Schreiber Stefan, Röcken Christoph
Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany.
Department of Pathology, Christian-Albrechts-University, Kiel, Germany.
Oncotarget. 2018 Dec 25;9(101):37497-37508. doi: 10.18632/oncotarget.26490.
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.
1580 primary CRCs were explored by immunohistochemistry for evaluation of VIR and EIR. Subgroup analyses included hybridization for IR isoform A (IR-A) and DNA mismatch repair protein immunohistochemistry. Clinico-pathological and survival parameters were studied.
High VIR was evident in 63.5% of all CRC samples and was associated with T-stage ( = 0.005). EIR was present in 72.2% and was associated with lower T-stages ( = 0.006) and UICC-stages ( < 0.001). EIR negativity was associated with increased metastasis ( 0.028), nodal spread ( < 0.001), lymphatic invasion ( 0.008) and a decreased tumor-specific ( 0.011) and overall survival ( 0.007; 95%-C.I.: 44.5-84.1). EIR negativity in UICC-stage II was associated with a significantly worse tumor-specific ( 0.045) and overall ( 0.043) survival. IR-A was expressed in CRC vessels and cells.
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.
癌症中的代谢重编程涉及胰岛素受体（IR），其在能量稳态和增殖过程中发挥作用。我们旨在表征结直肠癌中血管（VIR）和上皮（EIR）胰岛素受体的表达情况，并将其与临床病理参数及生存率相关联。
通过免疫组织化学对1580例原发性结直肠癌进行检测，以评估VIR和EIR。亚组分析包括IR同工型A（IR-A）的杂交以及DNA错配修复蛋白免疫组织化学。对临床病理和生存参数进行研究。
在所有结直肠癌样本中，63.5%呈现高VIR，且与T分期相关（P = 0.005）。72.2%存在EIR，且与较低的T分期（P = 0.006）和国际抗癌联盟（UICC）分期相关（P < 0.001）。EIR阴性与转移增加（P = 0.028）、淋巴结扩散（P < 0.001）、淋巴管浸润（P = 0.008）以及肿瘤特异性生存率降低（P = 0.011）和总生存率降低（P = 0.007；95%置信区间：44.5 - 84.1）相关。UICC II期患者中EIR阴性与显著更差的肿瘤特异性生存率（P = 0.045）和总生存率（P = 0.043）相关。IR-A在结直肠癌血管和细胞中表达。
我们证明VIR在结直肠癌中很常见，并将EIR阴性表征为一个重要的预后风险因素。对于UICC II期患者中EIR阴性与较差生存率之间的关联，应前瞻性评估其在治疗方案中的应用。
