Comparison of cytosolic p53 protein levels in the female genital tract and breast, and their tumors.

Under normal conditions, p53 protein is thought to maintain genomic stability. We measured this parameter in healthy tissues from female breast and genital tract using a quantitative, highly sensitive luminometric assay. An organ-specific pattern of p53 expression became evident: breast parenchyma (n = 40, median p53: 0.0346 ng/mg protein) and ovarian tissue (n = 12, 0.063 ng/mg) demonstrated markedly higher p53 levels than endometrium (n = 24, 0.0065 ng/mg), myometrium (n = 31, 0.005 ng/mg) or uterine cervix tissue (n = 25, 0. 002 ng/mg). Malignant tumors derived from these organs maintained the pattern of p53 expression with ovarian cancers (n = 14, median: 0.84 ng/mg) exceeding all other tissue types examined. Generally, p53 concentrations in malignant tumors, but also in uterine myomas were significantly higher than those in healthy controls. Breast cancer tissues, subgrouped according to prognostic parameters, demonstrated the highest p53 concentrations in samples with atypical histology, grading II-III, negative steroid receptors, and in cases of positive axillary lymph nodes. The frequency of elevated p53 concentrations in cancer cytosols, based on organ-specific normal concentrations, varied between 62% in breast cancers and 100% in cervical carcinomas. Uterine myomas showed 6% of elevated values. Grade II-III breast carcinomas overexpressed p53 more often than those with grading I (p < 0.05). In all carcinomas, the frequencies of overexpressed p53 protein markedly exceeded the frequencies of mutated p53 gene mutations reported in the literature. In conclusion, our data indicate that the extent of p53 expression and overexpression is organ dependent. When data of other studies on primary breast cancers are included, elevated levels of p53 protein in malignant tumors to some extent may indicate p53 gene mutations and worse prognosis if they exceed a higher threshold.

p53 determination in gynecological carcinomas: immunohistochemistry compared to luminometric immunoassay (LIA).

UNLABELLED: In gynecological carcinomas p53 overexpression has been associated with an aggressive tumor type and shorter overall survival. We compared p53 values analysed by a new quantitative luminometric immunoassay (LIA) applicable on tumor cytosol immunohistochemistry (IH). In 83 breast and 43 ovarian cancers p53 was analysed by LIA and IH (Byk-Sangtec, FRG) and by IH using monoclonal antibodies (MOAB/BP53-Bio Genex, FRG). In breast cancer 32 cases (39%) were immunohistochemically (IH) positive. LIA values ranged from 0.01 to 101 ng/mg protein (p), median (IH negative cases) = 0.208 and median (IH positives) = 0.857 ng/mg p. Using a cut off < 0.2 ng/mg p for a very low expression only 11% (3/27) were IH positive and > 0.8 for very high expression only 16% (3/20) were IH negative. In ovarian cancer values ranged from from 0.01 to 66.1 mg/mg p. 48.8% (21/43) were IH positive, median (IH negatives) = 0.234 and median (IH positives) = 1.43 ng/mg p. At a cut off < 0.2 ng/mg p 25% (3/12) were IH positive and at a cut off > 0.8 ng/mg p only 14% (2/14) were IH negative. CONCLUSION: The quantitative LIA determination of p53 in cytosols of gynecological carcinomas shows a good correlation to immunohistochemistry in cases of very high and very low expression.