Distinct subtypes of serous ovarian carcinoma identified by p53 determination.
OBJECTIVE
The overall prognosis of ovarian carcinoma is poor. However, the outcome of apparently similar cases is highly variable, and molecular markers that would predict disease outcome in a clinically useful manner are lacking. We investigated the value of p53 expression as a disease determinant in serous carcinoma, which is the most common type of ovarian carcinoma and has shown the highest frequency of p53 alterations.


METHODS
Tissue microarray constructed of 522 serous ovarian carcinomas was examined immunohistochemically using DO-7 monoclonal antibody against p53 protein. The findings were correlated with overall and disease-free survival, response to therapy, and clinicopathological characteristics of the patients.


RESULTS
Both excessive and completely negative p53 staining confered poor patient outcome and were considered aberrant p53 expression. Patients with aberrant p53 (59% of the carcinomas) showed 5-year overall survival of 26% (20-31%), whereas patients with normal p53 expression (41% of the carcinomas) showed 5-year overall survival of 79% (95% CI, 74-85%) (P < 0.0001). The association of aberrant p53 with poor prognosis was independent of clinicopathological parameters, e.g., stage and grade. In addition, aberrant p53 status was significantly associated with shorter disease-free survival (P < 0.0001) and poor response to therapy (P < 0.0001). In the most common subgroups, stage III and stage I carcinomas, 5-year overall survival rates for patients showing normal p53 vs. aberrant p53 were 72% vs. 19% (P < 0.0001) and 99% vs. 56% (P < 0.0001), respectively.


CONCLUSIONS
P53 expression status divides serous ovarian carcinomas into two distinct subtypes: one with a relatively good prognosis and the other with a particularly poor outcome.
Lassus
Heini
H
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Haartmaninkatu 2, 00290, Helsinki, Finland.
Leminen
Arto
A
Lundin
Johan
J
Lehtovirta
Pentti
P
Butzow
Ralf
R
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018284:Cystadenocarcinoma, Serous / Q000145:classification* / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000145:classification* / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D009944:Organoplatinum Compounds; D016159:Tumor Suppressor Protein p53