title: 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.
abstract: 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.
authors.affiliation: Department of Oncology, Radiumhemmet, Karolinska Institute and Hospital, Stockholm, Sweden. jenny.andersson@cck.ki.se
authors.forename: Jenny
authors.initials: J
authors.lastname: Andersson
authors.forename: Barbro
authors.initials: B
authors.lastname: Linderholm
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
authors.forename: Goran
authors.initials: G
authors.lastname: Elmberger
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases