Expression of p53 predicts treatment failure in aggressive non-Hodgkin's lymphomas.
Approximately 50% of patients with aggressive non-Hodgkin's lymphomas (NHL) achieve a complete remission (CR) and cure with combination chemotherapy. The International Index is a useful clinical measure that predicts the patients' tolerance of therapy and likelihood of achieving CR, but it is not a direct measure of chemosensitivity. In this study we have investigated the predictive value of the tumor suppressor gene, p53, as a biological marker for response to treatment in the aggressive NHL. A retrospective study was carried out on 50 patients with aggressive NHL who were treated with CHOP chemotherapy. Treatment outcome was correlated with the expression of p53 in the lymphoma, as measured by routine immunohistochemistry using the monoclonal antibody Do-7. Forty percent of the lymphomas had >5% of the cells staining positively for p53 and this finding correlated significantly with response to treatment. Fifty percent of patients with p53 positive tumors achieved a CR versus 77% of patients with p53 negative tumors. In addition, the relapse rate and time to relapse were significantly different in the two groups. In the p53 positive group, 60% of patients relapsed in a median time of 6 months, whereas 26% of the p53 negative group relapsed with the time to relapse being >22 months. The overall survival of the p53 positive group (17 months) was significantly shorter than that of p53 negative group (>24 months). These results suggest that the immunohistochemical assessment of p53 is a simple and important prognostic measure for patients with aggressive NHL who are treated with CHOP chemotherapy.
Navaratnam
S
S
Department of Internal Medicine, University of Manitoba, Manitoba Institute of Cell Biology, and the Manitoba Cancer Treatment and Research Foundation, Winnipeg, Canada.
Williams
G J
GJ
Rubinger
M
M
Pettigrew
N M
NM
Mowat
M R
MR
Begleiter
A
A
Johnston
J B
JB
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D016158:Genes, p53; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone