Immunofluorometric assay of p53 protein versus sequencing of p53 exons 5 to 9 for the detection of p53 abnormalities in ovarian carcinoma

p53 alteration, detected as mutation of rite p53 gene or as accumulation of mutant p53 protein, Is a common feature of most malignancies, including ov arian carcinoma, and may identify patients with unfavorable prognosis and r esistance to chemotherapy Tumor tissues from 55 patients with well or poorl y differentiated (grades I or 3) primary epithelial ovarian carcinoma were assessed both for p53 protein overexpression by a sensitive time-resolved i mmunofluorometric assay employing DO-I and CM-1 antibodies, and for genetic p53 abnormalities by dir ect sequencing of PCR-amplified exons 5 to 9. Six teen p53 mutations (29%), including 3 deletions causing frameshifts as well as one nonsense and 12 missense point mutations were found in all exons ex cept exon 9. Overexpression of p53 protein, defined as a concentration exce eding the 75th percentile, was found in 15 cases (27%), 10 of which had mis sense mutations (P<0.01). Tumors with nonsense and frameshift mutations wer e p53-negative by immunoassay. Both p53 mutation (P=0.04) and p53 protein a ccumulation (P<0.01) were associated with stage III-IV disease, while p53 m utation uas more closely related to grade 3 lesions (P=0.04) and serous his totype (P=0.01). These results indicate that p53 protein accumulation corre lates well with missense point mutation in carcinoma of the ovary anti, tog ether with other evidence that p53 abnormality may be prognostic of outcome in this disease suggest that the immunoassay of p53 protein may have clini cal value.