PAI-1 expression and its regulation by promoter 4G/5G polymorphism in clear cell renal cell carcinoma
- Authors
- Choi, Jung-Woo; Lee, Ju-Han; Park, Hong Seok; Kim, Young-Sik
- Issue Date
- 10월-2011
- Publisher
- B M J PUBLISHING GROUP
- Citation
- JOURNAL OF CLINICAL PATHOLOGY, v.64, no.10, pp.893 - 897
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CLINICAL PATHOLOGY
- Volume
- 64
- Number
- 10
- Start Page
- 893
- End Page
- 897
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/111507
- DOI
- 10.1136/jclinpath-2011-200182
- ISSN
- 0021-9746
- Abstract
- Aims To characterise patients with high plasminogen activator inhibitor-1 (PAI-1) expression as oral PAI-1 antagonists are currently in preclinical trials, and to determine whether the PAI-1 promoter 4G/5G polymorphism regulates PAI-1 expression in clear cell renal cell carcinoma (CCRCC). Methods PAI-1 expression was examined by immunohistochemistry in 69 CCRCC specimens. In addition, the promoter 4G/5G polymorphism was investigated by both allele-specific PCR and direct DNA sequencing. Results PAI-1 was overexpressed in 25/69 (36.2%) patients with CCRCC. PAI-1 staining was intense in tumour cells with a high Fuhrman nuclear grade and in spindle-shaped tumour cells. PAI-1 expression was significantly associated with older age at diagnosis (p = 0.027), high nuclear grade (p < 0.001), advanced clinical stage (p = 0.030) and distant metastasis (p = 0.009). In survival analyses, PAI-1 expression was correlated with disease-free survival in Kaplan-Meier curves (p = 0.015) but was not significant in the Cox hazards model (p = 0.527). The frequencies of the promoter polymorphism were 24.6% (17/69) 4G/4G, 43.5% (30/69) 4G/5G and 31.9% (22/69) 5G/5G. The homozygous 4G/4G or 5G/5G group showed a tendency for a high nuclear grade (p = 0.05) but the 4G/5G polymorphism was not related to other prognostic parameters. PAI-1 expression was poorly correlated with its promoter 4G/5G polymorphism (Spearman rho = 0.088). Conclusions CCRCC with high PAI-1 expression is characterised by older age, high nuclear grade, advanced stage, distant metastasis and/or shortened disease-free survival. PAI-1 expression is not affected by the promoter 4G/5G polymorphism.
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Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
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