Detection of cellular heterogeneity by DNA ploidy, 17 chromosome, and p53 gene in primary carcinoma and metastasis in a case of ovarian cancer.
An unusual case of a patient with ovarian carcinoma carrying the p53 point mutation in both metastases (omentum and lymph node), but not in the primary tumor, is described. The presence of a p53 single mutation (G:A) at the second base of codon 248 was examined by polymerase chain reaction-amplification refractory mutation system (PCR-ARMS) analysis. This case was examined also by fluorescent in situ hybrization (FISH) analysis and flow cytometry (FCM) to obtain further information at the single cell level and to detect heterogeneity within a population of cells. FCM analysis evidenced the same multiple aneuploid cell subpopulations in primary and in metastatic samples showing the presence of a cellular heterogeneity. FISH analysis showed a disomic condition for the 17 chromosome in the primary and in one metastasis, while in the other metastasis a monosomic together with a disomic subpopulation was revealed. Our results confirm the independent clonal evolution of the metastasis. The late mutation event observed only in metastatic specimens suggests the hypothesis that in the primary tumor the wild-type gene either does not perform its control role for unknown genetic structural events or the p53 gene in this case does not play a critical role in carcinogenesis.
Calugi
A
A
Obstetric and Gynaecologic Clinic, Tor Vergata University, Rome, Italy.
Eleuteri
P
P
Cavallo
D
D
Naso
G
G
Albonici
L
L
Lombardi
M P
MP
Manzari
V
V
Romanini
C
C
DeVita
R
R
D001483:Base Sequence; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000737:chemistry*; D004587:Electrophoresis, Agar Gel; D005260:Female; D005434:Flow Cytometry; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008969:Molecular Sequence Data; D009852:Omentum; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000556:secondary; D011003:Ploidies; D017354:Point Mutation; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm