The p53 protein is involved in several central cellular processes, includin
g gene transcription, DNA repair, cell cycling, genomic stability, chromoso
mal segregation, senescence, and apoptosis,p53 mutations frequently result
in an immunocytochemically detectable accumulation of the p53 protein in tu
mor cells. To evaluate whether p53 gene mutations are required for the onse
t of hematogeneous tumor cell dissemination, we compared the p53 status of
primary and micrometastatic tumor cells. Disseminated carcinoma cells could
be detected in bone marrow aspirates obtained from 46 (40%) of 114 patient
s with various types of epithelial tumors without overt skeleton metastases
, There was no correlation between the detection of p53 protein in primary
lung carcinomas and the presence of tumor cells in bone marrow. Further ana
lyses revealed that the disseminated carcinoma cells rarely accumulate muta
ted p53 protein and that 10 cell lines derived thereof did not harbor p53 m
utations even in the presence of such mutations in the autologous primary t
umors. These observations indicate that tumor cells can leave the primary t
umor before mutations of the p53 gene occur and that these mutations are no
t essential for such early hematogeneous dissemination of cancer cells. Thu
s, the value of mutated p53 as a target for diagnosis and treatment of micr
ometastatic disease in cancer patients is questionable.