Surgical Research Society of Southern Africa Presentation Breast Cancer: Comparing Estrogen and Her-2 Immunohistochemical Staining of Core and Excision Biopsy Specimens

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.

Download Full-text

0025 A comparative study of immunohistochemical staining and fluorescence in situ hybridization method of HER-2/neu in breast cancer

The Breast ◽

10.1016/s0960-9776(09)70074-8 ◽

2009 ◽

Vol 18 ◽

pp. S24

Author(s):

M. Koo ◽

B. Moon ◽

K. Choi ◽

C. Yom ◽

Y. Park

Keyword(s):

Breast Cancer ◽

In Situ Hybridization ◽

Comparative Study ◽

Fluorescence In Situ Hybridization ◽

Immunohistochemical Staining ◽

Hybridization Method ◽

Her 2

Download Full-text

Quantitative Assessment of HER-2/Neu Protein Concentration in Breast Cancer by Enzyme-Linked Immunosorbent Assay

The International Journal of Biological Markers ◽

10.1177/172460080301800103 ◽

2003 ◽

Vol 18 (1) ◽

pp. 13-20 ◽

Cited By ~ 18

Author(s):

V. Müller ◽

C. Thomssen ◽

C. Karakas ◽

I. Eustermann ◽

J. Ramirez Porras ◽

...

Keyword(s):

Breast Cancer ◽

Gene Amplification ◽

Immunosorbent Assay ◽

Immunohistochemical Staining ◽

Protein Concentration ◽

Tumor Tissue ◽

Enzyme Linked Immunosorbent Assay ◽

Cancer Tissue ◽

Tissue Extracts ◽

Her 2

Purpose The HER-2/neu protein (p185) has become a promising target for antibody therapy in breast cancer. We tested the feasibility of a quantitative approach for HER-2/neu testing based on the analysis of tumor tissue extracts by an enzyme-linked immunosorbent assay (ELISA). Experimental design Tumor tissue extracts of primary human breast cancers (n=124) were prepared using a triton-based buffer. HER-2/neu concentration was quantified by ELISA. Paraffin-embedded tissue sections of the same tumors were analyzed by immunohistochemical staining applying the monoclonal HER-2/neu antibody TAB 250 (n=124) and by chromogenic in situ hybridization (CISH) (n=73). Results Concentrations of p185 in tissue extracts determined by ELISA varied from 1 to 927 ng per mg protein with a median of 25 ng/mg protein, whereas normal breast tissue showed values from 0.4 to 5.5 ng/mg with a median of 2.2 ng/mg (p<0.0001, Mann-Whitney U test). A significant correlation between p185 concentration and immunohistochemical staining was observed (p<0.0001, Kruskal-Wallis test). In addition, p185 concentration measured by ELISA was correlated with the degree of HER-2/neu gene amplification determined by CISH. HER-2/neu-amplified tumors had significantly higher p185 concentrations (median value 181 ng/mg protein) than non-amplified tumors (median value 20 ng/mg; p<0.0001, Mann-Whitney U test). Conclusions ELISA-based measurement of HER-2/neu protein concentration in breast cancer tissue extracts is feasible and provides quantitative results for p185 protein concentrations that correlate closely with HER-2/neu immunoscore and gene amplification.

Download Full-text

Express Analysis of HER-2/NEU Status in Breast Cancer Biopsy Specimens

Bulletin of Experimental Biology and Medicine ◽

10.1007/s10517-013-2192-3 ◽

2013 ◽

Vol 155 (4) ◽

pp. 522-526 ◽

Cited By ~ 2

Author(s):

I. N. Nechaev ◽

E. N. Knyazev ◽

N. A. Krainova ◽

M. Yu. Shkurnikov

Keyword(s):

Breast Cancer ◽

Biopsy Specimens ◽

Express Analysis ◽

Her 2 ◽

Cancer Biopsy

Download Full-text

Reliance on Hormone Receptor Assays of Surgical Specimens May Compromise Outcome in Patients With Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2005.02.076 ◽

2005 ◽

Vol 23 (22) ◽

pp. 5148-5154 ◽

Cited By ~ 94

Author(s):

G. Bruce Mann ◽

Vanessa D. Fahey ◽

Frank Feleppa ◽

Malcolm R. Buchanan

Keyword(s):

Breast Cancer ◽

Hormone Receptor ◽

Core Biopsy ◽

Growth Factor Receptor ◽

Surgical Specimen ◽

Biopsy Specimens ◽

Her 2 ◽

Clinically Significant ◽

Receptor Assays ◽

Log Linear

Purpose To assess the concordance of breast cancer immunohistochemical receptor assays on core biopsy and surgical specimens. Patients and Methods We identified 100 patients whose core biopsy and definitive surgical specimens were processed in our hospital. New sections, with core and surgical specimens on the same slides, were stained for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) immunohistochemistry (IHC). Two pathologists assessed the sections independently. Raw scores and clinically significant groupings were compared. Results Concordance for ER, PR, overall hormone receptor (HR), and HER-2 status was seen in 86%, 83%, 90%, and 80% of patients, respectively. The core was positive, while the surgical specimen was negative in 13%, 11%, 9%, and 1% of patients, respectively. Using a log-linear model, differences in ER, PR, and HER-2 staining were all in the direction of stronger staining in the cores, and were statistically significant. Nine percent (95% CI, 4.2% to 16.4%) of women in this group would have had endocrine therapy inappropriately withheld if management decisions were based on surgical specimen results alone. Conclusion ER and PR assays on core biopsy specimens are more reliable than assays on surgical specimens. Receptor IHC should be performed on core biopsy specimens to avoid patients with HR positive cancers not receiving appropriate hormonal therapy and being overtreated with systemic chemotherapy. Biopsy should be considered in patients with “receptor negative” cancer and recurrent disease.

Download Full-text