Chromosome 11q13, c-erbB-2, and c-myc amplification in invasive breast carcinoma: clinicopathologic correlations.
To determine the frequency and clinicopathologic correlates of chromosome 11q13 amplification in breast carcinoma, DNA from 50 invasive tumors was analyzed by Southern blot hybridization using probes for the 11q13 loci bcl-1, PRAD1, hst1, EMS1, and GST-pi, as well as oncogenes c-erbB-2 and c-myc. Sixteen tumors (32%) were amplified for one or more loci. Seven tumors (14%) showed amplification of 11q13 loci; six of these were coamplified with either c-erbB-2 (three), c-myc (two), or both (one). Nine additional tumors (18%) were amplified for c-erbB-2, and three of these were coamplified with c-myc. None showed c-myc amplification alone. Tumors with 11q13 amplification showed equivalent degrees of bcl-1, PRAD1, hst1, and EMS1 amplification, delineating an approximately 800-kb amplicon. GST-pi was inconsistently amplified, evidence that it lies outside the amplicon defined by bcl-1 and EMS1. Amplification of 11q13 was unassociated with patient age, tumor size, axillary lymph node status, hormone receptors, DNA content, histologic grade, mitotic rate, nuclear pleomorphism, or tubule formation. c-myc amplification correlated with the lack of tubule formation (p = 0.04), whereas c-erbB-2 amplification correlated with axillary lymph node positivity (p = 0.04), high histologic grade (p = 0.003), increased nuclear pleomorphism (p = 0.008), and a high mitotic rate (p = 0.02). The frequency of coamplification of 11q13 loci, c-myc, and c-erbB-2 contradicts previous proposals that amplification of these genes occurs in independent subsets of breast carcinoma. Extended clinical followup will be necessary to determine whether 11q13 amplification has prognostic utility in invasive breast cancer.
Gaffey
M J
MJ
Department of Pathology, University of Virginia, School of Medicine, Charlottesville.
Frierson
H F
HF
Williams
M E
ME
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D016259:Genes, myc; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases
D066246:ErbB Receptors; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases