Prognostic value of apoptosis-related markers in urothelial cancer of the upper urinary tract

In Gab Jeong, Sung Han Kim, Hwang Gyun Jeon, Baek-Hui Kim, Kyung Chul Moon, Sang Eun Lee, Eunsik Lee

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

We investigated the expression of apoptosis-related markers and their association with the clinical outcomes of patients with urothelial carcinoma of the upper urinary tract. A total of 112 patients with urothelial carcinoma of the upper urinary tract that had surgery from March 1998 to July 2005 were included in the study. Tissue microarray slides were used for immunohistochemistry, and immunohistochemical staining was performed to investigate the association of apoptosis-related markers with clinical outcome. Apoptosis was confirmed by the TdT-mediated DUTP nick-end labeling method to obtain the apoptotic index. Survival analysis was performed according to the Kaplan-Meier method, and the Cox proportional hazard regression model was used to compare the relative influence of different prognostic factors. Among the 112 patients, 32 (28.6%) had altered expression of p53, 30 (26.8%) of bcl-2, 62 (55.4%) of bax, 27 (24.1%) of caspase-3, and 23 (20.5%) of survivin. The expression of p53 and caspase-3 was associated with the pathologic grade (P = .035 and P = .004, respectively). Altered expression of caspase-3 was associated with the pathologic stage (P = .016). The multivariate analysis showed that the expression of survivin (hazard ratio 2.91, 95% confidence interval 1.07-7.90, P = .036) and the apoptotic index (AI) (3.35, 1.06-10.56, P = .039), as well as the T and N stages (P = .043 and P = .010, respectively) were significantly associated with the disease-specific survival. Our results suggest that survivin expression and a high apoptotic index were poor prognostic factors for survival in patients with urothelial carcinoma of the upper urinary tract. These results may help to identify a subset of patients who require adjuvant therapy or closer follow-up.

Original languageEnglish
Pages (from-to)668-677
Number of pages10
JournalHuman Pathology
Volume40
Issue number5
DOIs
Publication statusPublished - 2009 May 1
Externally publishedYes

Fingerprint

Urologic Neoplasms
Apoptosis
Urinary Tract
Caspase 3
Carcinoma
Survival
Survival Analysis
Proportional Hazards Models
Multivariate Analysis
Biomarkers
Immunohistochemistry
Confidence Intervals
Staining and Labeling

Keywords

  • Apoptosis
  • Carcinoma
  • Kidney pelvis
  • Prognostic factor
  • Ureter

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Prognostic value of apoptosis-related markers in urothelial cancer of the upper urinary tract. / Jeong, In Gab; Kim, Sung Han; Jeon, Hwang Gyun; Kim, Baek-Hui; Moon, Kyung Chul; Lee, Sang Eun; Lee, Eunsik.

In: Human Pathology, Vol. 40, No. 5, 01.05.2009, p. 668-677.

Research output: Contribution to journalArticle

Jeong, In Gab ; Kim, Sung Han ; Jeon, Hwang Gyun ; Kim, Baek-Hui ; Moon, Kyung Chul ; Lee, Sang Eun ; Lee, Eunsik. / Prognostic value of apoptosis-related markers in urothelial cancer of the upper urinary tract. In: Human Pathology. 2009 ; Vol. 40, No. 5. pp. 668-677.
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AB - We investigated the expression of apoptosis-related markers and their association with the clinical outcomes of patients with urothelial carcinoma of the upper urinary tract. A total of 112 patients with urothelial carcinoma of the upper urinary tract that had surgery from March 1998 to July 2005 were included in the study. Tissue microarray slides were used for immunohistochemistry, and immunohistochemical staining was performed to investigate the association of apoptosis-related markers with clinical outcome. Apoptosis was confirmed by the TdT-mediated DUTP nick-end labeling method to obtain the apoptotic index. Survival analysis was performed according to the Kaplan-Meier method, and the Cox proportional hazard regression model was used to compare the relative influence of different prognostic factors. Among the 112 patients, 32 (28.6%) had altered expression of p53, 30 (26.8%) of bcl-2, 62 (55.4%) of bax, 27 (24.1%) of caspase-3, and 23 (20.5%) of survivin. The expression of p53 and caspase-3 was associated with the pathologic grade (P = .035 and P = .004, respectively). Altered expression of caspase-3 was associated with the pathologic stage (P = .016). The multivariate analysis showed that the expression of survivin (hazard ratio 2.91, 95% confidence interval 1.07-7.90, P = .036) and the apoptotic index (AI) (3.35, 1.06-10.56, P = .039), as well as the T and N stages (P = .043 and P = .010, respectively) were significantly associated with the disease-specific survival. Our results suggest that survivin expression and a high apoptotic index were poor prognostic factors for survival in patients with urothelial carcinoma of the upper urinary tract. These results may help to identify a subset of patients who require adjuvant therapy or closer follow-up.

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