Accuracy of HER2 status determination on breast core-needle biopsies (immunohistochemistry, FISH, CISH and SISH vs FISH).
Author(s): Arnould L, Roger P, Macgrogan G, Chenard MP, Balaton A, Beauclair S, Penault-Llorca F
Publication: Mod Pathol, 2012, Vol. 25, Page 675-82
PubMed ID: 22222637 PubMed Review Paper? No
Purpose of Paper
This paper examined the concordance of human epidermal growth factor receptor 2 (HER2) status in core needle biopsy (CNB) specimens as determined by immunohistochemistry (IHC) or silver in situ hybridization (SISH), fluorescent in situ hybridization (FISH), or chromogenic in situ hybridization (CISH) with HER2 status of matched surgical resection specimens as determined by FISH as well as the effect of IHC scoring method.
Conclusion of Paper
The concordance between HER2 status in the surgical specimens analyzed by FISH and that of the CNB was very high regardless of whether status was determined in the CNB by IHC, FISH, SISH or CISH. For all methods of analysis used, CNB specimens displayed high sensitivity (95-99%), specificity (97-98%), positive predictive value (PPV, 98-99%), and negative predictive values (95-99%) for HER2 status in the surgical specimens. CNB specimen also displayed low false positive (1-2%) and false negative rates (1-7%) for HER2 status in the surgical specimens. Some small, non-significant differences were observed among the IHC scoring methods and between the ISH visualization methods, but the Groupe d’Etude des Facteurs Pronostiques par Immunohistochimie dans le Cancer du Sein (GEFPICS) method resulted in fewer CNB and surgical specimens scoring as 2+ and more scoring as 0 than with the Pathologists’ scoring or the American Society of Clinical Oncology (ASCO) scoring methods.
Studies
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Study Purpose
This study investigated the effects of the analytical method (IHC, FISH, CISH, and SISH) used to determine HER2 status in CNB on the concordance with HER2 status in matched surgical resection specimens as determined by FISH. The effects of three IHC scoring methods on the concordance in HER2 scores between CNB and surgical resection specimens were also examined. Matched CNB and surgical resection specimens from 260 non-metastatic invasive breast carcinoma cases were obtained from 24 different centers over a 5-year period. CNB specimens were fixed in neutral-buffered formalin (NBF, 47-54% of specimens), alcohol-based fixatives containing formalin (38-50% of specimens), or Hollande’s-based fixative (4-6% of specimens). However, most surgical specimens were fixed in alcohol-based fixative containing formalin (56-60% of specimens) rather than NBF (35-40% of specimens), or the formalin-based Hollande’s fixative (4-6% of specimens). IHC was performed on CNB and surgical specimens for all 260 cases; CISH was performed on CNB for 259 cases, FISH was performed on 248 surgical resections and 251 CNB specimens, and SISH was performed for 182 CNB specimens. IHC scores were determined using three methods: the Herceptest (pathologists’ scoring) which has a cutoff of 10% for 3+category, the ASCO/CAP criteria which has a cutoff of 30% for 3+ category, and the GEFPICS criteria which has a cutoff of 60% of positive cells with intermediate intensity for the 2+ category.
Summary of Findings:
HER2 status in the surgical specimens by FISH was very strongly concordant with that in the CNB by IHC (κ=0.92-0.97 depending on the scoring method used), FISH (κ=0.99), SISH (κ=0.94) and CISH (κ=0.96). Importantly, all methods of CNB staining displayed high sensitivity (95-99%), specificity (97-98%), positive predictive value (PPV, 98-99%), and negative predictive values (95-99%) for the status in the surgical resection. CNB specimens also displayed low false positive (1-2%) and false negative rates (1-7%) for the HER2 status in the surgical resection, regardless of staining method. Although, the GEFPICS scoring method for IHC resulted in the lowest concordance in HER2 status between IHC-stained CNB and FISH-stained surgical specimens, the difference between this method and the other two scoring methods was not significant. Further, there were no significant differences in HER2 status of the FISH-stained surgical specimen and that of the CNB stained by FISH, SISH, or CISH. HER2 IHC staining of both surgical resection and CNB specimens was scored as 3+ in 50-51% of cases, regardless of scoring method used. However, when scored using the GEFPICS method, fewer CNB and surgical specimens were scored as 2+ (7% and 8%, respectively) than with the Pathologists’ scoring (17% and 19%, respectively) or the ASCO scoring (18% and 20%, respectively) and more CNB and surgical specimens were assigned a HER2 IHC staining score of 0 (30% and 29%, respectively) than with the Pathologists scoring (21% and 23%, respectively) or the ASCO scoring (18% and 21%, respectively).
Biospecimens
Preservative Types
- Formalin
- Other Preservative
- Ethanol
Diagnoses:
- Neoplastic - Carcinoma
Platform:
Analyte Technology Platform Protein Immunohistochemistry DNA In situ hybridization DNA FISH Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Biospecimen Acquisition Method of tissue acquisition Surgical resection
Core needle biopsy
FISH Specific Technology platform IHC
CISH
SISH
Immunohistochemistry Specific Data handling ASCO scoring
Pathologists scoring
GEFPICS scoring
In situ hybridization Specific Targeted nucleic acid HER2
Immunohistochemistry Specific Targeted peptide/protein HER2
FISH Specific Targeted nucleic acid HER2