Relationship of c-myc amplification to progression of breast cancer from in situ to invasive tumor and lymph node metastasis.
BACKGROUND
Amplification of the c-myc gene (also known as MYC) occurs in up to 20%-30% of breast cancers and has been associated with poor prognosis.


OBJECTIVE
The purpose of this study was to define the relationship between c-myc amplification and breast cancer progression in order to better understand the biological significance of c-myc amplification.


METHODS
We identified invasive tumors with grossly detectable c-myc amplification by using Southern blot analysis to examine frozen tissue from 135 breast carcinomas and polymerase chain reaction (PCR) analysis to examine archival paraffin-embedded tissue from an additional 19 invasive tumors. These 19 tumors were selected on the basis of histologically identifiable in situ and invasive components within the primary tumor and associated lymph node metastases. Amplification of c-myc in these areas was then assessed by quantitative PCR assay.


RESULTS
We detected gross c-myc amplification in 10 of the tumors examined--eight of the 135 frozen tissue specimens and two of the 19 archival specimens. We selected five of these 10 invasive tumors for further regional analysis. In all four cases where an in situ component was present, amplification of c-myc was present in both the in situ and the invasive components. However, c-myc amplification was present in the corresponding nodal metastases in only two of the four cases where this could be examined.


CONCLUSIONS
These results suggest that c-myc amplification can occur at an early stage in tumor progression and that amplification does not always persist in the nodal metastasis.
Department of Physiology, Faculty of Medicine, University of Manitoba, Canada.
P H
PH
Watson
J R
JR
Safneck
K
K
Le
D
D
Dubik
R P
RP
Shiu
D000328:Adult; D000368:Aged; D001483:Base Sequence; D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002278:Carcinoma in Situ / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D016258:Genes, mos / Q000235:genetics; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm