RELATIONSHIP OF C-MYC AMPLIFICATION TO PROGRESSION OF BREAST-CANCER FROM INSITU 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. Purpose: The purpose of this study was to define the relati onship between c-myc amplification and breast cancer progression in or der to better understand the biological significance of c-myc amplific ation. 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 addition al 19 invasive tumors. These 19 tumors were selected on the basis of h istologically 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. Resul ts: 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 s pecimens. We selected five of these 10 invasive tumors for further reg ional analysis. In all four cases where an in situ component was prese nt, amplification of c-myc was present in both the in situ and the inv asive components. However, c-myc amplification was present in the corr esponding nodal metastases in only two of the four cases where this co uld be examined. Conclusion: These results suggest that c-myc amplific ation can occur at an early stage in tumor progression and that amplif ication does not always persist in the nodal metastasis.