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.
Amir
Gail
G
Department of Pathology, Hadassah Medical Center and Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Issakov
Josephine
J
Meller
Isaac
I
Sucher
Erwin
E
Peyser
Amos
A
Cohen
Ian J
IJ
Yaniv
Isaac
I
Ben Arush
Myrian Weyl
MW
Tavori
Uri
U
Kollender
Yehuda
Y
Ron
Noemi
N
Peylan-Ramu
Nili
N
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002455:Cell Division; D002467:Cell Nucleus / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016017:Odds Ratio; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D012372:ROC Curve; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012512:Sarcoma, Ewing / Q000737:chemistry* / Q000401:mortality; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics
D019394:Ki-67 Antigen; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C000715470:MAS1 protein, human