Department of Histology, Faculty of Medicine, Medical University of Gdansk, 1 Debinki Street, Gdansk, 80211, Poland.
Department of Human Histology and Embryology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, Olsztyn, 10082, Poland.
BMC Cancer. 2023 Nov 14;23(1):1110. doi: 10.1186/s12885-023-11622-7.
Kidney renal clear cell carcinoma (KIRC) is the most common type of kidney cancer and its pathogenesis is strongly associated with VHL-HIF-VEGF signaling. SHH ligand is the upstream SHH pathway regulator, while GLI1 is its major effector that stimulates as a transcription factor, i.a. expression of VEGFA gene. The aim of present study was to assess the prognostic significance of SHH, GLI1 and VEGFA immunoreactivity in KIRC tissues. The analysis included paired tumor and normal samples from 34 patients with KIRC. The immunoreactivity of SHH, GLI1 and VEGFA proteins was determined by immunohistochemical (IHC) renal tissues staining. The IHC staining results were assessed using the immunoreactive score (IRS) method which takes into account the number of cells showing a positive reaction and the intensity of the reaction. Increased GLI1 protein immunoreactivity was observed in KIRC tissues, especially in early-stage tumors, according to the TNM classification. Elevated expression of the VEGFA protein was noted primarily in high-grade KIRC samples according to the Fuhrman/WHO/ISUP scale. Moreover, a directly proportional correlation was observed between SHH and VEGFA immunoreactivity in TNM 3 + 4 and Fuhrman/ISUP/WHO 3 + 4 tumor tissues as well as in samples of patients with shorter survival. We also observed an association between shorter patient survival as well as increased and decreased immunoreactivity, of the VEGFA and GLI1, respectively. The aforementioned findings suggest that the expression pattern of SHH, GLI1 and VEGFA demonstrates prognostic potential in KIRC.
肾透明细胞癌(KIRC)是最常见的肾癌类型,其发病机制与 VHL-HIF-VEGF 信号密切相关。SHH 配体是 SHH 通路的上游调节剂,而 GLI1 是其主要效应物,作为转录因子刺激 VEGFA 基因的表达。本研究旨在评估 KIRC 组织中 SHH、GLI1 和 VEGFA 免疫反应性的预后意义。分析包括 34 例 KIRC 患者的配对肿瘤和正常样本。通过免疫组织化学(IHC)肾组织染色来确定 SHH、GLI1 和 VEGFA 蛋白的免疫反应性。使用免疫反应性评分(IRS)方法评估 IHC 染色结果,该方法考虑了显示阳性反应的细胞数量和反应强度。根据 TNM 分类,在 KIRC 组织中观察到 GLI1 蛋白免疫反应性增加,尤其是在早期肿瘤中。根据 Fuhrman/WHO/ISUP 分级,观察到 VEGFA 蛋白在高级别 KIRC 样本中的表达升高。此外,在 TNM 3+4 和 Fuhrman/ISUP/WHO 3+4 肿瘤组织以及生存时间较短的患者样本中观察到 SHH 和 VEGFA 免疫反应性之间存在直接正相关。我们还观察到 VEGFA 和 GLI1 的免疫反应性增加和减少分别与患者生存时间缩短之间存在关联。上述发现表明,SHH、GLI1 和 VEGFA 的表达模式在 KIRC 中具有预后潜力。