In situ c-myc expression and genomic status of the c-myc locus in infiltrating ductal carcinomas of the breast.
We have studied the expression of the c-myc protooncogene and the cycle-dependent histone 4 gene at the cellular level by RNA:RNA in situ hybridization in 18 primary breast ductal adenocarcinomas. These tumors have previously been examined by Southern and Northern blot analysis for the genomic status of c-myc and its expression, respectively (Escot et al., Proc. Natl. Acad. Sci. USA, 83: 4834-4838, 1986). Positive c-myc hybridization signals were associated with carcinoma cells in all cases, including tumors which had no apparent alterations of the c-myc locus. Steady-state levels of c-myc mRNA appeared heterogeneous in carcinomas with similar histology. High levels of hybridization were found in four of seven tumors with strong amplification of the c-myc locus. Similarly high levels of c-myc hybridization were detected in two of nine cases which had an apparently normal c-myc locus but comparatively low cellularity. In addition to carcinoma cells, dense clusters of infiltrating lymphocytes, present in three tumors, exhibited c-myc hybridization. The expression of the histone 4 gene failed to correlate with levels of c-myc expression. We conclude that in infiltrating ductal carcinomas: (a) the c-myc protooncogene is transcriptionally activated; (b) c-myc amplification is probably underestimated due to heterogeneous cellularity; (c) high-level c-myc amplification is related to high-level expression, but other unknown factors also may play a role; (d) differences in levels of c-myc expression may not only be attributed to differences in the growth fractions; and (e) c-myc mRNA in total RNA from biopsy samples may be contributed by infiltrating lymphocytes.
Mariani-Costantini
R
R
Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Escot
C
C
Theillet
C
C
Gentile
A
A
Merlo
G
G
Lidereau
R
R
Callahan
R
R
D001943:Breast Neoplasms / Q000235:genetics*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics*; D002453:Cell Cycle; D002874:Chromosome Mapping; D005260:Female; D005784:Gene Amplification; D006801:Humans; D009693:Nucleic Acid Hybridization; D011519:Proto-Oncogenes; D014158:Transcription, Genetic