The Role of PD-1 Positivity in the Tumour Nest on Clinical Outcome in Upper Tract Urothelial Carcinoma Patients Treated with Radical Nephroureterectomy

Aims: The role of PD-1 (programmed cell death 1) expression on the clinical outcome of upper tract urothelial carcinoma has not yet been elucidated in detail. Materials and methods: PD-1 expression was immunohistochemically examined in 181 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy. A part of PD-1 protein expression in the tumour periphery and tumour nest was evaluated separately. The PD-1-positive cells were counted in the area showing the highest density of PD-1 expression at a magnification of 400 X. Results: PD-1 staining in the tumour nest was low in 137 (75.7%) and high in 44 (24.3%) patients. PD-1 staining in the tumour periphery was low in 78 (43.1%) and high in 103 (56.9%) patients. The 5 year progression-free survival rates in patients with the high PD-1 expression in the tumour nest and in the tumour periphery were 54.6% and 67.7%, respectively, which were significantly lower than those in their counterparts (79.4%, P < 0.001; 80.0%, P = 0.04). The 5 year cancer-specific survival rates in patients with the high PD-1 expression in the tumour nest and the tumour periphery were 69.1% and 75.7%, respectively, which were significantly lower than those in their counterparts (84.7%, P = 0.007; 87.8%, P = 0.01). A multivariate Cox regression analysis identified the high PD-1 expression in the tumour nest (hazard ratio 3.07, P < 0.001; hazard ratio 2.44, P = 0.011) and positive lymphovascular invasion (hazard ratio 4.86, P < 0.001; hazard ratio 4.03, P < 0.001) as independent predictors of disease progression and of cancer death, respectively. Conclusions: PD-1 positivity in the tumour nest could be a strong predictor for a worse clinical outcome and may be a useful indicator for selecting appropriate candidates for adjuvant therapy such as chemotherapy in upper tract urothelial carcinoma patients treated with radical nephroureterectomy. (C) 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.