4.4 Article

Prognostic value of programmed death ligand 1, p53, and Ki-67 in patients with advanced-stage colorectal cancer

Journal

HUMAN PATHOLOGY
Volume 71, Issue -, Pages 20-29

Publisher

W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.humpath.2017.07.014

Keywords

Colorectal cancer; Prognosis; Biomarkers; PD-L1; p53; Ki-67 labeling index

Categories

Funding

  1. Science and Technology Commission of Shanghai Municipality [15495810300]
  2. National Natural Science Foundation of China [81071791, 81401963]

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Current prognostic indicators are ineffective for identifying advanced-stage colorectal cancer (CRC) patients with high risk of recurrence after surgical resection. We investigated the prognostic value of p53, Ki-67, and programmed death ligand 1 (PD-L1) in 254 patients with stage II and III CRC. The expression of p53 was positive in 63% of cases. Up-regulation of p53 was associated with smaller tumor size (P = .001) and higher Ki-67 labeling index (LI) (P = .031). The tumor Ki-67 LI was high (>= 20%) in 197 (78%) of the patients. High Ki-67 LI was associated with higher TNM stage (P = .031), positive p53 expression (P = .031), and negative PD-L1 expression (P = .003). The 5-year relapse-free survivals (RFS) were 53% and 89%, respectively, for the p53-positive and Ki-67 LI-high patients and the p53-negative and Ki-67 LI-low patients (P < .001). In univariate analysis, negative p53 (P = .001), low Ki-67 LI (P = .006), low PD-L1 expression (P=.044), low TNM stage (P < .001), rectosigmoid location (P = .026), and small size (P = .013) were significantly related to RFS. In multivariate Cox regression analysis, positive p53 expression (hazard ratio [HR]: 2.48; 95% confidence interval: 1.34-4.59, P = .004), high Ki-67 LI (HR, 2.62; 95% CI, 1.12-6.14, P = .027) and high TNM stage (HR, 2.598; 95% CI, 1.55-4.37, P < .001,) were independent predictors of unfavorable prognosis. In summary, PD-L1, Ki-67, and p53 staining individually had significant prognostic value for patients with stage II and III CRC. Moreover, combining p53 H-score >= 35 and Ki-67 LI >= 20% identifies patients with poor clinical outcome. (C) 2017 Elsevier Inc. All rights reserved.

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