HER-2/neu (c-erbB-2) evaluation in primary breast carcinoma by fluorescent in situ hybridization and immunohistochemistry with special focus on intratumor heterogeneity and comparison of invasive and in situ components

Appl Immunohistochem Mol Morphol. 2004 Mar;12(1):14-20. doi: 10.1097/00129039-200403000-00003.


We have studied the intratumor HER-2/neu heterogeneity in 78 consecutive and population-based primary invasive breast carcinomas. Within the invasive component, heterogeneity was detected in only 1 of 78 tumors. In 48 tumors (62%), we found both in situ and invasive components in analyzed tissue sections. Twelve of these 48 tumors had a difference of at least 2 arbitrary units in the in situ compared with the invasive part of the tumor with regard to the HER-2/neu status analyzed by HercepTest (immunohistochemistry). Eight of these 12 tumors were reanalyzed with fluorescent in situ hybridization and immunohistochemistry with and without a new Automated Cellular Imaging System. In this limited material, immunohistochemistry in combination with the Automated Cellular Imaging System seemed to have a better correlation with fluorescent in situ hybridization than immunostaining analyzed manually. In conclusion, HER-2/neu expression is not seldom heterogeneous in invasive compared with in situ components within a tumor. This finding should be considered in the choice of evaluation method. To avoid heterogeneity as a confounding factor in HER-2/neu analyses, detection methods such as immunohistochemistry and fluorescent in situ hybridization, which can provide evaluation in a preserved tissue architecture, should be used. Perhaps the intratumor HER-2/neu heterogeneity can explain some of the unexpected failures of trastuzumab therapy.

Publication types

  • Comparative Study
  • Evaluation Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line
  • Humans
  • Immunohistochemistry / methods*
  • In Situ Hybridization, Fluorescence / methods*
  • Receptor, ErbB-2 / metabolism*


  • Receptor, ErbB-2