Aljabery Firas, Shabo Ivan, Gimm Oliver, Jahnson Staffan, Olsson Hans
Department of Urology, and Department of Clinical and Experimental Medicine, Medical Faculty, Linköping University, SE 581 85, Linköping, Sweden.
Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery (MMK), Karolinska Institutet, SE 171 77, Stockholm, Sweden. Department of Breast, Endocrine and Sarcoma Surgery, Karolinska University Hospital, SE 171 76, Stockholm, Sweden.
Urol Oncol. 2018 Dec;36(12):530.e7-530.e18. doi: 10.1016/j.urolonc.2018.05.025. Epub 2018 Oct 24.
We investigated the effects of alterations in the biological markers p14, p53, p21, and p16 in relation to tumour cell proliferation, T-category, N- category, lymphovascular invasion, and the ability to predict prognosis in patients with muscle-invasive bladder cancer (MIBC) treated with cystectomy and, if applicable, chemotherapy.
We prospectively studied patients with urinary bladder cancer pathological stage pT1 to pT4 treated with cystectomy, pelvic lymph node dissection and postoperative chemotherapy. Tissue microarrays from paraffin-embedded cystectomy tumour samples were examined for expression of immunostaining of p14, p53, p21, p16 and Ki-67 in relation to other clinical and pathological factors as well as cancer-specific survival.
The median age of the 110 patients was 70 years (range 51-87 years), and 85 (77%) were male. Pathological staging was pT1 to pT2 (organ-confined) in 28 (25%) patients and pT3 to pT4 (non-organ-confined) in 82 (75%) patients. Lymph node metastases were found in 47 patients (43%). P14 expression was more common in tumours with higher T-stages (P = 0.05). The expression of p14 in p53 negative tumours was associated with a significantly shorter survival time (P=0.003). Independently of p53 expression, p14 expression was associated with an impaired response to chemotherapy (P=0.001). The expression of p21 in p53 negative tumours was associated with significantly decrease levels of tumour cell proliferation detected as Ki-67 expression (P=0.03).
The simultaneous expression of the senescence markers involved in the p53-pathway shows a more relevant correlation to the pathological outcome of MIBC than each protein separately. P14 expression in tumours with non-altered (p53-) tumours is associated with poor prognosis. P14 expression is associated with impaired response to chemotherapy. P21 expression is related to decreased tumour cell proliferation.
我们研究了生物标志物p14、p53、p21和p16的改变与肿瘤细胞增殖、T分期、N分期、淋巴血管侵犯以及预测接受膀胱切除术且（如适用）化疗的肌层浸润性膀胱癌（MIBC）患者预后能力之间的关系。
我们前瞻性地研究了接受膀胱切除术、盆腔淋巴结清扫术和术后化疗的病理分期为pT1至pT4的膀胱癌患者。对石蜡包埋的膀胱切除肿瘤样本制作的组织微阵列进行检查，以检测p14、p53、p21、p16和Ki-67的免疫染色表达，并分析其与其他临床和病理因素以及癌症特异性生存的关系。
110例患者的中位年龄为70岁（范围51 - 87岁），其中85例（77%）为男性。病理分期为pT1至pT2（器官局限性）的患者有28例（25%），pT3至pT4（非器官局限性）的患者有82例（75%）。47例患者（43%）发现有淋巴结转移。p14表达在T分期较高的肿瘤中更常见（P = 0.05）。p53阴性肿瘤中p14的表达与显著缩短的生存时间相关（P = 0.003）。独立于p53表达，p14表达与化疗反应受损相关（P = 0.001）。p53阴性肿瘤中p21的表达与以Ki-67表达检测到的肿瘤细胞增殖水平显著降低相关（P = 0.03）。
参与p53通路的衰老标志物的同时表达与MIBC的病理结果的相关性比每种蛋白质单独的相关性更显著。p53未改变（p53-）的肿瘤中p14表达与预后不良相关。p14表达与化疗反应受损相关。p21表达与肿瘤细胞增殖减少相关。
