Abstract
Recent studies have demonstrated a consistent inverse relationship between oestrogen receptor (ER) and epidermal growth factor receptor (EGFR) levels in female human breast cancer. Serial cross-section studies have suggested that separate populations of ER+/EGFR- and ER-/EGFR+ cancer cells exist in tumours deemed by immunocytochemical assay (ICA) to be positive for both. We have developed a dual ICA that is able to stain for both ER and EGFR on a single 5 microns frozen section sample of breast tissue. Twenty-two samples of female human breast cancer tissue that exhibited positivity for ER and EGFR by ER-ICA using the H222 monoclonal antibody and EGFR-ICA using the EGFR1 monoclonal antibody underwent the dual ICA. There was a significant correlation in receptor positivity between the single and dual assays for both ER (rs = 0.801, P < 0.001) and EGFR (rs = 0.831, P < 0.001). Individual cancer cells exhibited one of three staining patterns: nuclear staining only (ER+/EGFR-), membrane-associated and cytoplasmic staining only (ER-/EGFR+) or no staining (ER-/EGFR-). No cancer cells exhibited both nuclear and membrane/cytoplasmic staining. This is the first description of a simultaneous dual immunocytochemical assay system for ER and EGFR in clinical breast cancer specimens. The results suggest that ER and EGFR expression are mutually exclusive within an individual breast cancer cell in vivo with separate populations of ER+/EGFR- cells, ER-/EGFR+ cells and ER-/EGFR- cells coexisting.
Highlights
This inverse relationship with all its implications for prognosis has been the subject of intense study
The technique of taking serial cross-section samples is open to the criticism that the same cell or cell groups are not being examined in different sections. To address this issue we have developed a dual immunocytochemical assay (D-ICA) that is able to stain for both ER and epidermal growth factor receptor (EGFR) on a single 5 jLm frozen section sample of tumour cell lines (Sharma et al, 1994)
The tissues used for analysis were obtained from 22 patients who had previously been categorised to be positive for ER and EGFR by immunocytochemical assay
Summary
This inverse relationship with all its implications for prognosis has been the subject of intense study. Initial investigations involved the use of biochemical ligand-binding assays and revealed that ER could be detected in 60-80% of human breast cancers (McGuire et al, 1975) and EGFR in 45% (Klijn et al, 1992). These studies involved the homogenisation of sample tissue and were unable to address the issues of tumour heterogeneity, such as which cells were receptor positive (e.g. benign or malignant) or what proportion of cancer cells were receptor positive. The development of monoclonal antibodies and immunocytochemical assays specific for ER (King & Greene, 1984) and EGFR (Waterfield et al, 1982) on frozen sections addressed these issues. The EGFR immunocytochemical assay (EGFRICA) using the monoclonal antibody EGFR1 (Waterfield et al, 1982) localises EGFR on the cellular membrane and this displays a heterogeneous distribution (Toi et al, 1989)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
