The expression pattern of Ku correlates with tumor radiosensitivity and disease free survival in patients with rectal carcinoma

Cancer. 2002 Sep 15;95(6):1199-205. doi: 10.1002/cncr.10807.

Abstract

Background: Preoperative radiotherapy reduces the rate of local recurrence and improves the chance of survival in patients with resectable, advanced rectal carcinoma. However, because not all tumors respond similarly to radiation, sorting out suitable patients is required to irradiate tumors rationally. The authors examined the possible role of Ku protein in determining tumor radiosensitivity and disease free survival in patients with rectal carcinoma.

Methods: The authors studied 96 patients with advanced rectal carcinoma. In preradiation biopsy specimens of tumor samples, the number of cells that were stained positive for Ku protein was evaluated by immunohistochemistry. The expression pattern of Ku protein was examined for an association between tumor radiosensitivity (which was determined according to T classification downstaging, complete pathologic response, or Response Evaluation Criteria in Solid Tumors) and disease free survival.

Results: There was a high degree of correlation between the percentage of cells that expressed the 70-kDa Ku protein (Ku70) and the 86-kDa Ku protein (Ku86) in the tumor sections (correlation coefficient = 0.85; P < 0.001). The expression pattern of Ku protein was correlated not only with tumor radiosensitivity but also with disease free survival. Pathologic TMN classification, histopathologic grade, and Ku70 expression were significant prognostic variables for disease free survival in a multivariate analysis (P = 0.0031, P = 0.030, and P = 0.023, respectively).

Conclusions: Ku70 and Ku86 raise the predictive possibility of tumor radiosensitivity. Ku may be a useful parameter for selecting patients with rectal carcinoma for preoperative radiotherapy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Nuclear*
  • DNA Helicases*
  • DNA-Binding Proteins / analysis*
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Ku Autoantigen
  • Male
  • Middle Aged
  • Nuclear Proteins / analysis*
  • Prognosis
  • Radiation Tolerance / physiology*
  • Rectal Neoplasms / chemistry
  • Rectal Neoplasms / mortality*
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / radiotherapy*

Substances

  • Antigens, Nuclear
  • DNA-Binding Proteins
  • Nuclear Proteins
  • DNA Helicases
  • XRCC5 protein, human
  • Xrcc6 protein, human
  • Ku Autoantigen