Cortactin is associated with tumour progression and poor prognosis in prostate cancer and SIRT2 other than HADC6 may work as facilitator in situ

J Clin Pathol. 2012 Dec;65(12):1088-96. doi: 10.1136/jclinpath-2012-200940. Epub 2012 Sep 3.

Abstract

Objective: Cortactin acts as a prominent substrate of histone deacetylases (HDACs) and plays important roles in tumour progression in several human cancers. However, the clinical significance of its expression in human prostate cancer (PCa) has not been determined. We aimed to identify the potential role of cortactin expression in tumour progression and prognosis in PCa and the association with HDACs.

Methods: 256 foci with distinctive lesions in 110 prostate specimens were collected to identify the status of among cortactin, SIRT2, histone deacetylase 6 (HDAC6) by immunohistochemistry and its relationship with clinicopathological and follow-up data were analysed.

Results: The results showed that cortactin expression was significantly higher (79.1%), and SIRT2 expression was lower (37.3%) in PCa foci, when it was compared with high-grade prostatic intraepithelial neoplasia foci and benign foci, respectively. HDAC6 expression was low and had no statistical significance in PCa. High intensity of cortactin staining was significantly and independently associated with a high prostate-specific antigen (PSA) level, high Gleason score, clinical stage progression and shortened survival time in patients with PCa. High intensity of SIRT2 staining was significantly and independently associated with a high PSA level, old age, high Gleason score and clinical stage progression. Multivariable Cox regression analysis showed cortactin expression was a significant prognostic factor for survival of patients with PCa (β, 0.736; 95% CI 1.371 to 3.181; p=0.001).

Conclusions: The results suggested that cortactin seems to be a satisfactory marker to predict tumour progression and survival in cases of PCa. And it may be SIRT2 rather than HADAC6 is responsible for tumour occurrence and the progression of PCa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Cortactin / metabolism*
  • Disease Progression
  • Histone Deacetylase 6
  • Histone Deacetylases / metabolism*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Prognosis
  • Prostate / metabolism*
  • Prostate / pathology
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Sirtuin 2 / metabolism*

Substances

  • Biomarkers, Tumor
  • Cortactin
  • SIRT2 protein, human
  • Sirtuin 2
  • HDAC6 protein, human
  • Histone Deacetylase 6
  • Histone Deacetylases