HER2 Testing: Central Laboratory Assessment of HER2-Equivocal (2+ Staining) Samples Using IHC and Dual SISH
Gabriela I Acosta Haab, Isabel L Frahm, Sandra I Sarancone, Maria C Horsburgh. Hospital de Oncologia Marie Curie, Caba, Buenos Aires, Argentina; Sanatorio Mater Dei, Caba, Buenos Aires, Argentina; Laboratorio Quantum Clinica de Diagnostico Medico, Rosario, Santa Fe, Argentina; Productos Roche SAQeI, Tigre, Buenos Aires, Argentina
Background: In breast cancer overexpression or amplification of HER2 is associated with higher metastatic risk and shorter overall survival. In these patients, however, therapies targeting HER2 prolong overall, progression-free and disease-free survival. Immunohistochemistry (IHC) is the method most frequently used to assess HER2 overexpression, but equivocal results (2+) have to be further studied in order to classify them as positive or negative.
Design: In August 2003 a network of Pathology Laboratories trained in HER2 assessment by IHC was set up in Argentina, supervised in turn by an Advisory Board (AB) made up of a Coordinator and two consultants. Regular training and internal and external quality control (performed by Nordicq) ensure standardization and reproducibility of results. External Laboratories submit samples with scores of 2+ to one of three laboratories of the AB for re-testing with IHC and/or study of gene amplification by in situ hybridization (ISH) techniques. We report here the results of 74 equivocal samples that we received and re-tested with IHC and the novel Dual SISH Ventana Kit.
Results: Of the 74 initially equivocal samples, upon re-testing by IHC 40 (54%) were scored as 3+, and 39 showed HER2 gene amplification by Dual SISH (in 29 cases amplification was high). The remaining sample produced an error. Twenty one samples (28%) were either negative or 1+, and none of these showed gene amplification. The rest of the initially equivocal samples (i.e. 13- 18%) were classified as 2+. Of these, only 6 had gene amplification (high in 2 cases).
Conclusions: Accurately identifying HER2 positive tumours allows for correct decision making regarding therapy of breast cancer. Equivocal cases by IHC must be further studied in order to clarify HER2 status. In our experience, even with properly trained and quality-controlled Pahtology laboratories, repeating IHC centrally can positively categorize up to 82% of initially equivocal samples, leaving just 18% for ISH techniques. Optimizing IHC results is important because ISH techniques are more costly, and are less widely available. There is a high degree of overall concordance between central ICH and central SISH.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 38, Tuesday Afternoon