Discrimination between multicentric and multifocal carcinomas of the breast through clonal analysis.
BACKGROUND
An unanswered, important question concerning multiple breast carcinomas is whether they arise independently in the breast (multicentric) or are metastatic deposits from a single, primary carcinoma (multifocal). This issue was studied by clonal analysis of each focus of multiple breast carcinomas.


METHODS
First, the clonality of 30 breast carcinomas was analyzed by the method based on restriction fragment length polymorphism of the X-chromosome-linked phosphoglycerokinase (PGK) gene and on random inactivation of the gene. Second, the clonality of each focus of three multiple breast carcinomas was analyzed by the same method.


RESULTS
Clonal analysis of the 30 breast carcinomas revealed that every carcinoma was monoclonal in origin, and one of two alleles of the PGK gene was inactivated at random in these carcinomas. Three patients with multiple breast carcinomas had three, three, and four histologically separate foci of carcinoma in the breast, respectively. Clonal analysis showed that each focus was monoclonal in origin and, in addition, the same allele of the PGK gene was inactivated consistently at each focus in every patient.


CONCLUSIONS
The thesis that multiple carcinoma foci arise independently is unlikely to be true, because the probability that every independent focus happens to inactivate the same allele of PGK gene in every patient is very low. It seems more likely that a single primary carcinoma spreads throughout the breast to culminate in multiple secondary carcinoma foci. Therefore, it is concluded that multiple breast carcinomas are multifocal and not multicentric in origin.
Noguchi
S
S
Department of Surgery, Center for Adult Diseases, Osaka, Japan.
Aihara
T
T
Koyama
H
H
Motomura
K
K
Inaji
H
H
Imaoka
S
S
D001943:Breast Neoplasms / Q000473:pathology*; D002874:Chromosome Mapping; D002999:Clone Cells; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D009362:Neoplasm Metastasis; D010735:Phosphoglycerate Kinase / Q000235:genetics; D016133:Polymerase Chain Reaction; D014960:X Chromosome
D010735:Phosphoglycerate Kinase