A comparison of HER2/neu gene amplification and its protein overexpression between primary breast cancer and metastatic lymph nodes.
OBJECTIVE
Breast cancer is a heterogeneous disease. The aim of this prospective study, in which fluorescence in situ hybridization was used to determine human epidermal growth factor receptor 2 status in primary breast cancers and in the lymph node metastases, was to verify the stability of human epidermal growth factor receptor 2 status in the following steps of neoplastic progression of breast cancer, which is fundamental for an appropriate therapeutic approach.


METHODS
From patients with primary breast cancer, for whom, after January 2003, surgery was performed and involved metastatic lymph nodes were found, we randomly selected four groups of 15 patients, whose human epidermal growth factor receptor 2 score by immunohistochemistry was either 0, 1+, 2+ or 3+, respectively, totaling to 60. For each of those patients, their primary tumors and all of the metastatic lymph nodes were examined. Primary tumors and metastatic lymph nodes in each patient were examined by fluorescence in situ hybridization.


RESULTS
Of 18 patients with fluorescence in situ hybridization-positive primary tumors, 15 (83.3%) were fluorescence in situ hybridization-positive and 2 (11.1%) were fluorescence in situ hybridization-negative in all of their metastatic lymph nodes, and 1 (5.5%) patient had mixed (fluorescence in situ hybridization-positive or -negative) metastatic lymph nodes. Of 42 patients with fluorescence in situ hybridization-negative primary tumors, 40 (95%) were fluorescence in situ hybridization-negative and 2 (5%) fluorescence in situ hybridization-positive in all of their metastatic lymph nodes.


CONCLUSIONS
This study revealed that fluorescence in situ hybridization resulted in a high concordance of 83.3% between the human epidermal growth factor receptor 2 manifestation (fluorescence in situ hybridization-positive status) in primary tumors and that in metastatic lymph nodes, demonstrating that it is appropriate to determine whether and how to apply treatment by trastuzumab based on the results of evaluation of human epidermal growth factor receptor 2 expression.
Aoyama
Kei
K
Department of Surgery II, Tokyo Women's Medical University, Tokyo, Japan. k-aoyama@surg2.twmu.ac.jp
Kamio
Takako
T
Nishikawa
Toshio
T
Kameoka
Shingo
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human