Change of HER‐2/neu status in a subset of distant metastases from breast carcinomas

It is assumed that HER‐2/neu status remains consistent in breast carcinoma during metastatic spread, but in most previous studies primary tumours were compared with concurrent regional lymph node metastases. The present study investigated 31 breast carcinomas and their corresponding lymph node and distant metastases for HER‐2/neu status by immunohistochemistry (HercepTest™) and fluorescence in situ hybridization (FISH) (PathVysion™). In 14 cases, serum HER‐2/neu (SHER‐2) was measured sequentially using the Bayer Immuno 1™ HER‐2/neu assay. Comparing HER‐2/neu immunohistochemistry of primary tumours and distant metastases case by case, increased HER‐2/neu expression was found in the distant metastases in 15 cases (48.4%), three (9.7%) of which showed an increase from score 0 to score 3+. In contrast, lymph node metastases showed the same HER‐2/neu expression as the primary tumours, confirmed by FISH. Two cases, which showed HER‐2/neu score 3+ and HER‐2/neu amplification in the primary tumours, revealed increased SHER‐2 levels above 50 ng/ml at the first measurement. Five of the 14 cases (36%) showed an increase of SHER‐2 above 50 ng/ml towards the end of the patients' life. On the basis of these results, there is evidence that in a subset of breast carcinomas, HER‐2/neu amplification and overexpression occur de novo in distant metastases at a late disease stage. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

[1]  J. Price.  Metastasis from human breast cancer cell lines , 2005, Breast Cancer Research and Treatment.

[2]  P. Heikkilä,et al.  Mannose receptor (MR) and common lymphatic endothelial and vascular endothelial receptor (CLEVER)-1 direct the binding of cancer cells to the lymph vessel endothelium. , 2003, Cancer research.

[3]  H. Sewell,et al.  The production and characterisation of a chimaeric human IgE antibody, recognising the major mite allergen Der p 1, and its chimaeric human IgG1 anti-idiotype , 2002, Molecular pathology : MP.

[4]  D. Larsimont,et al.  Comparison of HER-2 status between primary breast cancer and corresponding distant metastatic sites. , 2002, Annals of oncology : official journal of the European Society for Medical Oncology.

[5]  D. Larsimont,et al.  Reliability of the tissue microarray based FISH for evaluation of the HER-2 oncogene in breast carcinoma. , 2002, Journal of clinical pathology.

[6]  R. Xu,et al.  Amplification of Her-2/neu Gene in Her-2/neu-Overexpressing and -Nonexpressing Breast Carcinomas and Their Synchronous Benign, Premalignant, and Metastatic Lesions Detected by FISH in Archival Material , 2002, Modern Pathology.

[7]  A. Thor.  Are patterns of HER-2/neu amplification and expression among primary tumors and regional metastases indicative of those in distant metastases and predictive of Herceptin response? , 2001, Journal of the National Cancer Institute.

[8]  H. Moch,et al.  Patterns of her-2/neu amplification and overexpression in primary and metastatic breast cancer. , 2001, Journal of the National Cancer Institute.

[9]  J. Isola,et al.  Amplification of HER-2/neu and topoisomerase IIalpha in primary and metastatic breast cancer. , 2001, Cancer research.

[10]  D. Chan,et al.  Clinical utility of serum HER-2/neu testing on the Bayer Immuno 1 automated system in breast cancer. , 2001, Anticancer research.

[11]  T. Mcclanahan,et al.  Involvement of chemokine receptors in breast cancer metastasis , 2001, Nature.

[12]  L. Krogerus,et al.  HER-2/neu oncogene expression in advanced breast cancer. , 2001, Cancer detection and prevention.

[13]  A. Dnistrian,et al.  Monitoring Therapy by Serum HER-2/Neu , 2000, The International journal of biological markers.

[14]  M. Bui,et al.  Assessment of Her-2/neu overexpression in primary breast cancers and their metastatic lesions: an immunohistochemical study. , 2000, Annals of clinical and laboratory science.

[15]  C. Shimizu,et al.  c‐erbB‐2 protein overexpression and p53 immunoreaction in primary and recurrent breast cancer tissues , 2000, Journal of surgical oncology.

[16]  K. Kinzler,et al.  Genetic instability and darwinian selection in tumours. , 1999, Trends in cell biology.

[17]  J. Fletcher,et al.  HER-2/neu (c-erb-B2) gene and protein in breast cancer. , 1999, American journal of clinical pathology.

[18]  S. Hirohashi,et al.  Multiple developmental pathways of highly aggressive breast cancers disclosed by comparison of histological grades and c‐erbB‐2 expression patterns in both the non‐invasive and invasive portions , 1998, Pathology international.

[19]  T. Shankey,et al.  Common patterns of genetic evolution in human solid tumors. , 1997, Cytometry.

[20]  R. Zeillinger,et al.  Tissue expression and serum levels of HER-2/neu in patients with breast cancer. , 1997, Oncology.

[21]  D. Slamon,et al.  HER‐2/neu Signal Transduction in Human Breast and Ovarian Cancer , 1997, Stem cells.

[22]  T. Singleton,et al.  Stability of HER-2/neu expression over time and at multiple metastatic sites. , 1993, Journal of the National Cancer Institute.

[23]  L. Demers,et al.  Elevated soluble c-erbB-2 antigen levels in the serum and effusions of a proportion of breast cancer patients. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  D. Pinkel,et al.  ERBB2 amplification in breast cancer analyzed by fluorescence in situ hybridization. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[25]  J. Price.  The biology of metastatic breast cancer , 1990, Cancer.

[26]  S. Naber,et al.  Strategies for the analysis of oncogene overexpression. Studies of the neu oncogene in breast carcinoma. , 1990, American journal of clinical pathology.

[27]  N. Lemoine,et al.  Absence of activating transmembrane mutations in the c-erbB-2 proto-oncogene in human breast cancer. , 1990, Oncogene.

[28]  D. Altman,et al.  An immunohistochemical evaluation of c-erbB-2 expression in human breast carcinoma. , 1988, British Journal of Cancer.

[29]  W. McGuire,et al.  Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. , 1987, Science.