Expression of p53 gene product and cell proliferation marker Ki-67 in Ewing's sarcoma: correlation with clinical outcome.

Overexpression of tumor suppressor gene p53, cell proliferation nuclear antigen Ki-67, and proto-oncogene HER-2/neu are associated with poor prognosis in some tumors. We studied p53, Ki-67, and HER-2/neu immunohistochemical expression in archival biopsies of 37 patients with Ewing's sarcoma (ES). Patients with ES were treated at four Israeli hospitals between 1982 and 2000. Formalin-fixed paraffin-embedded tissue sections were stained by immunohistochemistry for p53, Ki-67, and HER-2/neu. More than 300 cells were counted on each slide, and the percentage of positively stained nuclei was computed. p53 overexpression was defined as nuclear staining of >2.3% of cells, Ki-67 overexpression as nuclear staining of >8.3% malignant cells. HER-2/neu staining was scored semiquantitatively on a scale of 0 to 4+. Twenty-two of 37 patients are alive and well, with mean follow-up time of 38 months. There was overexpression of p53 in 16 patients (43%) and of Ki-67 in 21 patients (57%). The correlation between p53 and Ki-67 overexpressions was 0.61. We found no overexpression of HER-2/neu. Median relapse-free survival (RFS) was statistically significantly shorter for patients with p53 overexpression (25 months) than for patients with negative staining (>92 months). The prognostic value of p53 overexpression was also significant after adjusting for tumor location and age. Median RFS was shorter for patients with positive Ki-67 staining (40 months) than for patients with negative staining (80 months) but did not reach statistical significance. Our study suggests that p53 is a predictor of RFS in patients with ES. More patients must be studied to assess the validity of this observation. Copyright 2002, Elsevier Science (USA). All rights reserved.