Es. Lianidou et al., Immunofluorometric assay of p53 protein versus sequencing of p53 exons 5 to 9 for the detection of p53 abnormalities in ovarian carcinoma, ANTICANC R, 19(1B), 1999, pp. 749-756
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.