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.
Westhof
G
G
Department of Obstetrics and Gynecology, University of Witten/Herdecke School of Medicine, Witten, Germany. westhof@t-online.de
Bader
W
W
Greiner-Mai
E
E
Hatzmann
W
W
D001940:Breast / Q000737:chemistry* / Q000166:cytology / Q000473:pathology; D001943:Breast Neoplasms / Q000737:chemistry* / Q000175:diagnosis / Q000473:pathology; D002277:Carcinoma / Q000737:chemistry / Q000175:diagnosis / Q000473:pathology; D003600:Cytosol / Q000737:chemistry*; D005260:Female; D005833:Genital Neoplasms, Female / Q000737:chemistry* / Q000175:diagnosis / Q000473:pathology; D005836:Genitalia, Female / Q000737:chemistry* / Q000166:cytology / Q000473:pathology; D006801:Humans; D007889:Leiomyoma / Q000737:chemistry / Q000175:diagnosis / Q000473:pathology; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D009928:Organ Specificity; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000175:diagnosis / Q000473:pathology; D010053:Ovary / Q000737:chemistry / Q000166:cytology / Q000473:pathology; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics; D014594:Uterine Neoplasms / Q000737:chemistry / Q000175:diagnosis / Q000473:pathology; D014599:Uterus / Q000737:chemistry / Q000166:cytology / Q000473:pathology
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53