Significance of c-erbB-2 amplification and DNA aneuploidy. Analysis in 78 patients with node-negative breast cancer.
BACKGROUND
Amplification of the c-erbB-2 protooncogene and DNA aneuploidy have been reported to correlate with poor patient prognosis in human breast cancer. Several studies have investigated the prognostic value of these two factors in heterogeneous populations of patients with node-positive and node-negative disease. This study evaluated, on a series of patients with node-negative disease, whether c-erbB-2 proto-oncogene amplification and cellular DNA content could identify a subset of patients who, without adjuvant therapy, are destined to experience a relapse.


METHODS
Paraffin-embedded tissues of 78 patients were evaluated for cellular DNA content using flow cytometric analysis. Amplification of c-erbB-2 was determined on the same group of patients using slot-blot hybridization. The majority of patients were matched with control subjects for the following five clinicopathologic criteria: size of primary tumor, menopausal status, estrogen receptor, anniversary year of initial treatment, and age at treatment. Long-term follow-up (5-16 years) was available for each patient, none of whom received any form of adjuvant therapy.


RESULTS
The presence of an abnormal DNA stemline was found in 47% (37 of 78) of the tissue specimens, whereas only 10% (8 of 78) of the tumors expressed from 3-fold to 22-fold c-erbB-2 amplification. Combined c-erbB-2 amplification and DNA aneuploidy occurred in a small group of patients (n = 4), all of whom experienced relapse. The four remaining tumors having excessive gene copy numbers had a diploid DNA distribution.


CONCLUSIONS
The results indicate that tumors that overexpress the c-erbB-2 proto-oncogene have variable amounts of DNA and that c-erbB-2 amplification and DNA ploidy analysis provide limited predictive information of relapse in patients with node-negative breast cancer. Although the combination of c-erbB-2 amplification and DNA aneuploidy may be a predictor of poor prognosis in a small number of patients, neither measurement alone is effective in identifying patients at increased risk of recurrence of disease.
Babiak
J
J
Department of Laboratory Medicine, Cross Cancer Institute, Edmonton, Alberta, Canada.
Hugh
J
J
Poppema
S
S
D000782:Aneuploidy; D001943:Breast Neoplasms / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics*; D004171:Diploidy; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases
D004273:DNA, Neoplasm; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human