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PAI-1 expression and its regulation by promoter 4G/5G polymorphism in clear cell renal cell carcinoma
  1. Jung-Woo Choi1,
  2. Ju-Han Lee1,
  3. Hong Seok Park2,
  4. Young-Sik Kim1
  1. 1Department of Pathology, Korea University Ansan Hospital, Ansan, Korea
  2. 2Department of Urology, Korea University Ansan Hospital, Ansan, Korea
  1. Correspondence to Professor Young-Sik Kim, Department of Pathology, Korea University Ansan Hospital, 516, Gojan-1 Dong, Danwon-Gu, Ansan-Si, Gyeonggi-Do, 425-707, Republic of Korea; apysk{at}korea.ac.kr

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 ρ=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.

  • Renal cancer
  • immunohistochemistry
  • cytokines
  • uropathology
  • tumour virology
  • lymph node pathology

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Footnotes

  • Funding This study was supported by Korea University grant number K1031641 for academic purposes.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Ethics approval was provided by the research ethics committee of Korea University Ansan Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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