Afonso Julieta, Longatto-Filho Adhemar, DA Silva Vitor Moreira, Amaro Teresina, Santos Lúcio L
Life and Health Sciences Research Institute (ICVS), School of Healh Sciences (ECS) University of Minho, Braga 4710-057, Portugal ; ICVS/3B's, PT Government Associate Laboratory, Braga 4710-057/Guimarães 4806-909, Portugal.
Life and Health Sciences Research Institute (ICVS), School of Healh Sciences (ECS) University of Minho, Braga 4710-057, Portugal ; ICVS/3B's, PT Government Associate Laboratory, Braga 4710-057/Guimarães 4806-909, Portugal ; Laboratory of Medical Investigation (LIM 14), Faculty of Medicine, São Paulo State University, São Paulo 01246-000, Brazil ; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo 14784-400, Brazil.
Oncol Lett. 2014 Oct;8(4):1447-1454. doi: 10.3892/ol.2014.2392. Epub 2014 Jul 30.
Urothelial bladder carcinoma (UBC) is heterogeneous in its pathology and clinical behaviour. Evaluation of prognostic and predictive biomarkers is necessary, in order to produce personalised treatment options. The present study used immunohistochemistry to evaluate UBC sections containing tumour and non-tumour areas from 76 patients, for the detection of p-mTOR, CD31 and D2-40 (blood and lymphatic vessels identification, respectively). Of the non-tumour and tumour sections, 36 and 20% were scored positive for p-mTOR expression, respectively. Immunoexpression was observed in umbrella cells from non-tumour urothelium, in all cell layers from non-muscle-invasive (NMI) tumours (including expression in superficial cells), and in spots of cells from muscle-invasive (MI) tumours. Positive expression decreased from non-tumour to tumour urothelium, and from pT1/pTis to pT3/pT4 tumours; however, the few pT3/pT4 positive cases had worse survival rates, with 5-year disease-free survival being significantly lower. Angiogenesis occurrence was impaired in pT3/pT4 tumours that did not express p-mTOR. In conclusion, p-mTOR expression in non-tumour umbrella cells is likely a reflection of their metabolic plasticity, and extension to the inner layers of the urothelium in NMI tumours is consistent with an enhanced malignant potential. The expression in cell spots in a few MI tumours and absence of expression in the remaining tumours is intriguing and requires further research. Additional studies regarding the up- and downstream effectors of the mTOR pathway should be conducted.
尿路上皮膀胱癌(UBC)在病理和临床行为上具有异质性。评估预后和预测生物标志物对于制定个性化治疗方案是必要的。本研究采用免疫组织化学方法,对76例患者的包含肿瘤和非肿瘤区域的UBC切片进行评估,以检测磷酸化哺乳动物雷帕霉素靶蛋白(p-mTOR)、CD31和D2-40(分别用于识别血管和淋巴管)。在非肿瘤和肿瘤切片中,p-mTOR表达阳性率分别为36%和20%。在非肿瘤尿路上皮的伞细胞、非肌层浸润性(NMI)肿瘤的所有细胞层(包括表层细胞表达)以及肌层浸润性(MI)肿瘤的细胞斑点中均观察到免疫表达。从非肿瘤尿路上皮到肿瘤尿路上皮,以及从pT1/pTis到pT3/pT4肿瘤,阳性表达均降低;然而,少数pT3/pT4阳性病例的生存率较差,5年无病生存率显著降低。在不表达p-mTOR的pT3/pT4肿瘤中,血管生成受到损害。总之,非肿瘤伞细胞中p-mTOR的表达可能反映了它们的代谢可塑性,NMI肿瘤中尿路上皮内层的延伸与恶性潜能增强一致。少数MI肿瘤中细胞斑点的表达以及其余肿瘤中无表达的情况很有趣,需要进一步研究。应开展关于mTOR通路上下游效应器的更多研究。