ABSTRACT
Accurate assessment of HER-2/neu gene status in breast cancer patients has important prognostic and therapeutic implications. Overexpression/gene amplification of HER-2 is associated with a more aggressive clinical course and eligibility for targeted therapy with trastuzumab. A variety of immunohistochemical (IHC) antibodies and in situ hybridisation (ISH) methods have been employed to assess HER-2 status. SP3 is a rabbit monoclonal antibody that has been shown to have a high level of agreement with other anti-HER-2 antibodies and ISH methods. We assessed HER-2 status by SP3 and HercepTest IHC stains and by fluorescence in situ hybridisation (FISH) on invasive breast carcinomas from paired needle core biopsy and excisional biopsy specimens from 100 patients. We compared the two antibodies with respect to concordance rates with FISH, concordance rates between samples of the same tumour, and sensitivity and specificity using FISH as the reference test. Concordance between SP3 and FISH in needle core biopsy and excisional biopsy specimens was 96% (95% CI 91.9% to 99.7%) (κ=0.89 (95% CI 0.73 to 1.00)) and 97% (95% CI 90.3% to 99.3%) (κ=0.84 (95% CI 0.66 to 1.00)), respectively. Sensitivity and specificity of SP3 for detecting HER-2 overexpression/gene amplification were 78.3% and 100%, respectively, in needle core biopsy and excisional biopsy specimens. Concordance between SP3 results assessed on the needle core biopsy and excisional biopsy was 89% (95% CI 81.2% to 94.4%) (κ=0.62 (95% CI 0.42 to 0.82)). Concordance between SP3 and HercepTest antibodies, after excluding 2+ cases, was 97.6% (95% CI 94.0% to 99.3%) (κ=0.88 (95% CI 0.77 to 1.00)). SP3 is a reliable alternative to HercepTest in evaluating HER-2 status in breast cancer patients. Like other anti-HER-2 antibodies, SP3 may serve as a diagnostic tool in breast pathology and has potential utility as an IHC biomarker in non-mammary malignancies.
Subject(s)
Biomarkers, Tumor/analysis , Breast Neoplasms/genetics , Receptor, ErbB-2/analysis , Sp3 Transcription Factor/analysis , Female , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Receptor, ErbB-2/genetics , Sensitivity and Specificity , Sp3 Transcription Factor/geneticsABSTRACT
BACKGROUND: Low-grade adenosquamous carcinoma (LGASC) is an uncommon variant of metaplastic carcinomas of the breast. The immunohistochemical profile of this entity has not been well characterized and is likely because of its seemingly inconsistent staining patterns when commonly used immunohistochemical stains are employed. We set out to further elucidate the immunohistochemical profile of this uncommon entity in a sizable cohort of patients. MATERIALS AND METHODS: Thirty cases of LGASC were identified in our files. Commonly used immunohistochemical stains such as myoepithelial and cytokeratin markers used to evaluate a small glandular proliferation in the breast (the differential diagnosis of which includes LGASC) were utilized. The pattern and location of immunoreactivity were recorded in each case. Results were compared for staining trends. RESULTS: All cases of LGASC demonstrated variable staining in both lesional glands and stromal cells for myoepithelial (p63, smooth muscle myosin, smooth muscle actin, CD10, calponin) and cytokeratin (CK AE1/3, CK5/6, CK7, CK 34ßE12, Cam 5.2) markers. Within a single case, circumferential staining using myoepithelial markers was complete, discontinuous, and absent in over a third of the studied cases. A minority of cases showed either complete circumferential staining (or complete absence) by any single immunohistochemical stain. Lamellar staining of stromal cells surrounding glands was best highlighted using smooth muscle myosin heavy chain or calponin. Using cytokeratin stains, core staining (luminal glandular cells demonstrating distinctly stronger staining intensity than the basally located cells in the same gland) was observed in approximately half of the studied cases. These lesional stromal cells were negative for all cytokeratins, with the exception of 1, which was focally positive for 1 cytokeratin immunostain (CK7) while being negative for 3 others. CONCLUSIONS: LGASC consistently stains in an inconsistent manner using commonly used immunohistochemical stains. In addition, we found lamellar staining and core staining using myoepithelial and cytokeratin stains, respectively, to be distinctive and therefore diagnostically valuable.
