HER-2/neu amplification and overexpression in primary human breast cancer is associated with early metastasis.
The etiology of human breast cancer is poorly understood and no specific marker of transformation has been identified. Amplification of HER-2/neu, as reported in a comprehensive study by Slamon et al, was found to be the most powerful predictor of disease-free and overall survival after the status of the axillary lymph nodes. Our study examines the HER-2/neu oncogene in 61 primary human breast cancers at both the DNA level (by Southern blotting) and the protein level (by immunohistochemical methods). Of the 61 tumors analyzed in our study, 17 (28%) had amplification of HER-2/neu. There was no significant correlation of HER-2/neu amplification with age, tumor diameter or hormone receptor status; however, amplification and overexpression of HER-2/neu was significantly correlated with the status of the axillary lymph nodes (P = 0.02). Of 16 patients with amplification of HER-2/neu, 14 (88%) had positive regional nodes. One of the two node negative cases with amplified HER-2/neu had bone marrow micrometastasis. Overall, 16 out of 17 (94%) tumors of the patients having amplified HER-2/neu had metastatic disease at the time of diagnosis. In summary, HER-2/neu amplification is associated with early tumor dissemination in primary human breast cancer and may be a marker of poor prognosis.
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, N.Y. 10021.
R K
RK
Tiwari
P I
PI
Borgen
G Y
GY
Wong
C
C
Cordon-Cardo
M P
MP
Osborne
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D004247:DNA / Q000032:analysis; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D009362:Neoplasm Metastasis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases
D004247:DNA; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases