scholarly journals Concordance and Proportion of Equivocal Results of Silver-Enhanced <i>In Situ</i> Hybridization and Immunohistochemical Technique for the Determination of HER2 Amplification in Breast Cancer Patients

2014 ◽  
Vol 2 (2) ◽  
pp. 37-43
Author(s):  
Soon Ha Kwon ◽  
Deuk Young Lee ◽  
Jong Eun Lee ◽  
Jihyoun Lee ◽  
Sun Wook Han ◽  
...  
Heliyon ◽  
2021 ◽  
pp. e07558
Author(s):  
Yahdiana Harahap ◽  
Athalia Theda Tanujaya ◽  
Farhan Nurahman ◽  
Aurelia Maria Vianney ◽  
Denni Joko Purwanto

2006 ◽  
Vol 17 (3) ◽  
pp. 424-428 ◽  
Author(s):  
L. Mercatali ◽  
V. Valenti ◽  
D. Calistri ◽  
S. Calpona ◽  
G. Rosti ◽  
...  

2018 ◽  
Vol 6 (4) ◽  
pp. 593-599 ◽  
Author(s):  
Magdalena Bogdanovska-Todorovska ◽  
Slavica Kostadinova-Kunovska ◽  
Rubens Jovanovik ◽  
Blagica Krsteska ◽  
Goran Kondov ◽  
...  

BACKGROUND: Accurate assessment of HER-2 is imperative in selecting patients for targeted therapy. Most commonly used test methods for HER-2 are immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). We evaluated the concordance between FISH and IHC for HER-2 in breast cancer samples using Food and Drug Administration approved tests.MATERIAL AND METHODS: Archived paraffin tissue blocks from 73 breast cancer patients were used. HER-2 immunostaining was performed using Ventana anti–HER-2 monoclonal antibody. The FISH assay was performed using PathVysion™ HER-2 DNA Probe Kit.RESULTS: Of the 73 cases 68.5% were IHC 0/1+, 15.07% were IHC 2+ and 16.44% were IHC 3+. Successful hybridisation was achieved in 72 cases. HER-2 FISH amplification was determined in 16.67% cases. Ten IHC 3+ and two IHC 2+ cases were FISH positive. Two of the IHC 3+ cases were FISH negative. Concordance rate was 100%, 18.18% and 83.33% for IHC 0/1+, 2+ and 3+ group, respectively. Total concordance was 84.72%, kappa 0.598 (p < 0.0001). The sensitivity of IHC in detecting IHC 2+ and IHC 3+ cases was 16.7% and 83.3%, and the specificity was 85% and 96.67%, respectively.CONCLUSION: The consistency between the methods was highest for IHC negative and lowest for IHC equivocal cases. The immunohistochemistry showed high sensitivity for IHC 2+/3+ cases and high specificity for IHC 3+ cases. Our results support the view that false-positive rather than false-negative IHC results are a problem with HER-2/IHC testing, and that IHC should be used as an initial screening test, but IHC 2+/ 3+ results should be confirmed by FISH.


2005 ◽  
Vol 23 (19) ◽  
pp. 4287-4297 ◽  
Author(s):  
Lynn G. Dressler ◽  
Donald A. Berry ◽  
Gloria Broadwater ◽  
David Cowan ◽  
Kelly Cox ◽  
...  

Purpose HER2 is a clinically important tumor marker in breast cancer; however, there is controversy regarding which method reliably measures HER2 status. We compared three HER2 laboratory methods: immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR), to predict disease-free survival (DFS) and overall survival (OS) after adjuvant doxorubicin-based therapy in node-positive breast cancer patients. Methods This is a Cancer and Leukemia Group B (CALGB) study, using 524 tumor blocks collected from breast cancer patients registered to clinical trial CALGB 8541. IHC employed CB11 and AO-11-854 monoclonal antibodies; FISH used PathVysion HER2 DNA Probe kit; PCR utilized differential PCR (D-PCR) methodology. Results Cases HER2 positive by IHC, FISH and D-PCR were 24%, 17%, and 18%, respectively. FISH and IHC were clearly related (κ = 64.8%). All three methods demonstrated a similar relationship for DFS and OS. By any method, for patients with HER2-negative tumors, there was little or no effect of dose of adjuvant doxorubicin-based therapy. For patients with HER2-positive tumors, all three methods predicted a benefit from dose-intense (high-dose) compared with low- or moderate-dose adjuvant doxorubicin-based therapy. Conclusion FISH is a reliable method to predict clinical outcome following adjuvant doxorubicin-based therapy for stage II breast cancer patients. There is a moderate level of concordance among the three methods (IHC, FISH, PCR). None of the methods is clearly superior. Although IHC-positive/FISH-positive tumors yielded the greatest interaction with dose of therapy in predicting outcome, no combination of assays tested was statistically superior.


2006 ◽  
Vol 24 (34) ◽  
pp. 5373-5380 ◽  
Author(s):  
Gaynor J. Bates ◽  
Stephen B. Fox ◽  
Cheng Han ◽  
Russell D. Leek ◽  
José F. Garcia ◽  
...  

Purpose To assess the clinical significance of tumor-infiltrating FOXP3-positive regulatory T cells (TR) in breast cancer patients with long-term follow-up. Patients and Methods FOXP3-positive TR were detected by immunohistochemistry with our new, extensively characterized FOXP3 monoclonal antibody, 236A/E7. Numbers of FOXP3-positive lymphocytes in tissue microarray cores from pure ductal carcinoma in situ (DCIS; n = 62), invasive breast cancer (n = 237) or from comparable areas of normal terminal duct lobular breast tissue (n = 10) were determined. A median cutoff of ≥ 15 defined patients with high numbers of TR. Results TR numbers were significantly higher in in situ and invasive breast carcinomas than in normal breast; invasive tumors have significantly higher numbers than DCIS (P = .001). High numbers of FOXP3-positive TR identified patients with DCIS at increased risk of relapse (P = .04) and patients with invasive tumors with both shorter relapse-free (P = .004) and overall survival (P = .007). High TR numbers were present in high-grade tumors (P ≤ .001), in patients with lymph node involvement (P = .01), and in estrogen receptor (ER) –negative tumors (P = .001). Importantly, high numbers of TR within ER-positive tumors identified high-risk patients (P = .005). Unlike conventional clinicopathologic factors, high numbers of FOXP3-positive TR can identify patients at risk of relapse after 5 years. Conclusion These findings indicate that quantification of FOXP3-positive TR in breast tumors is valuable for assessing disease prognosis and progression, and that TR are an important therapeutic target for breast cancer. FOXP3-positive TR represent a novel marker for identifying late-relapse patients who may benefit from aromatase therapy after standard tamoxifen treatment.


2013 ◽  
Vol 66 (5) ◽  
pp. 409-414 ◽  
Author(s):  
Timothy Michael D'Alfonso ◽  
Yi-Fang Liu ◽  
Zhengming Chen ◽  
Ying-Bei Chen ◽  
Ashley Cimino-Mathews ◽  
...  

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.


1999 ◽  
Vol 45 (8) ◽  
pp. 1206-1213 ◽  
Author(s):  
Anders N Pedersen ◽  
Nils Brünner ◽  
Gunilla Høyer-Hansen ◽  
Peter Hamer ◽  
David Jarosz ◽  
...  

Abstract Background: The complex between urokinase (uPA) and its type-1 inhibitor (PAI-1) is formed exclusively from the active forms of these components; thus, the complex concentration in a biological sample may reflect the ongoing degree of plasminogen activation. Our aim was to establish an ELISA for specific quantification of the uPA:PAI-1 complex in plasma of healthy donors and breast cancer patients. Methods: A kinetic sandwich format immunoassay was developed, validated, and applied to plasma from 19 advanced-stage breast cancer patients, 39 age-matched healthy women, and 31 men. Results: The assay detection limit was &lt;2 ng/L, and the detection of complex in plasma was validated using immunoabsorption, competition, and recovery tests. Eighteen cancer patients had a measurable complex concentration (median, 68 ng/L; range, &lt;16 to 8700 ng/L), whereas for healthy females and males the median signal values were below the detection limit (median, &lt;16 ng/L; range, &lt;16 to 200 ng/L; P &lt;0.0001). For patient plasma, a comparison with total uPA and PAI-1 showed that the complex represented a variable, minor fraction of the uPA and PAI-1 concentrations of each sample. Conclusion: The reported ELISA enables detection of the uPA:PAI-1 complex in blood and, therefore, the evaluation of the complex as a prognostic marker in cancer.


Sign in / Sign up

Export Citation Format

Share Document