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

Lisha Wang, Zebing Liu, Kurt W. Fisher, Fei Ren, Jiaojie Lv, Darrell Davidson, Lee A. Baldridge, Xiang Du, Liang Cheng

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)20-29
Number of pages10
JournalHuman Pathology
Volume71
DOIs
StatePublished - Jan 1 2018

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Colorectal Neoplasms
Ligands
Recurrence
Survival
Neoplasms
Up-Regulation
Regression Analysis
Confidence Intervals
Staining and Labeling

Keywords

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Prognostic value of programmed death ligand 1, p53, and Ki-67 in patients with advanced-stage colorectal cancer. / Wang, Lisha; Liu, Zebing; Fisher, Kurt W.; Ren, Fei; Lv, Jiaojie; Davidson, Darrell; Baldridge, Lee A.; Du, Xiang; Cheng, Liang.

In: Human Pathology, Vol. 71, 01.01.2018, p. 20-29.

Research output: Contribution to journalArticle

Wang, Lisha ; Liu, Zebing ; Fisher, Kurt W. ; Ren, Fei ; Lv, Jiaojie ; Davidson, Darrell ; Baldridge, Lee A. ; Du, Xiang ; Cheng, Liang. / Prognostic value of programmed death ligand 1, p53, and Ki-67 in patients with advanced-stage colorectal cancer. In: Human Pathology. 2018 ; Vol. 71. pp. 20-29.
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abstract = "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.",
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T1 - Prognostic value of programmed death ligand 1, p53, and Ki-67 in patients with advanced-stage colorectal cancer

AU - Wang, Lisha

AU - Liu, Zebing

AU - Fisher, Kurt W.

AU - Ren, Fei

AU - Lv, Jiaojie

AU - Davidson, Darrell

AU - Baldridge, Lee A.

AU - Du, Xiang

AU - Cheng, Liang

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

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