HER2 testing on core needle biopsy specimens from primary breast cancers: interobserver reproducibility and concordance with surgically resected specimens

Abstract

Background: Accurate evaluation of human epidermal growth factor receptor type-2 (HER2) status based on core needle biopsy (CNB) specimens is mandatory for identification of patients with primary breast cancer who will benefit from primary systemic therapy with trastuzumab. The aim of the present study was to validate the application of HER2 testing with CNB specimens from primary breast cancers in terms of interobserver reproducibility and comparison with surgically resected specimens.

Methods: A total of 100 pairs of archival formalin-fixed paraffin-embedded CNB and surgically resected specimens of invasive breast carcinomas were cut into sections. All 100 paired sections were subjected to HER2 testing by immunohistochemistry (IHC) and 27 paired sections were subjected to that by fluorescence in situ hybridization (FISH), the results being evaluated by three and two observers, respectively. Interobserver agreement levels in terms of judgment and the concordance of consensus scores between CNB samples and the corresponding surgically resected specimens were estimated as the percentage agreement and κ statistic.

Results: In CNB specimens, the percentage interobserver agreement of HER2 scoring by IHC was 76% (κ = 0.71) for 3 × 3 categories (0-1+ versus 2+ versus 3+) and 90% (κ = 0.80) for 2 × 2 categories (0-2+ versus 3+). These levels were close to the corresponding ones for the surgically resected specimens: 80% (κ = 0.77) for 3 × 3 categories and 92% (κ = 0.88) for 2 × 2 categories. Concordance of consensus for HER2 scores determined by IHC between CNB and the corresponding surgical specimens was 87% (κ = 0.77) for 3 × 3 categories, and 94% (κ = 0.83) for 2 × 2 categories. Among the 13 tumors showing discordance in the mean IHC scores between the CNB and surgical specimens, the results of consensus for FISH results were concordant in 11. The rate of successful FISH analysis and the FISH positivity rate in cases with a HER2 IHC score of 2+ differed among specimens processed at different institutions.

Conclusion: It is mandatory to study HER2 on breast cancers, and either CNB or surgical specimen can be used.

Figure 1

Cases with concordant judgment of HER2 score between CNB and surgically resected specimens. A-B. Case 3: HER2 score for both the CNB specimen (A) and the surgically resected specimen (B) was 3+. C-D. Case 22: HER2 score for both the CNB specimen (C) and the surgically resected specimen (D) was 2+. E-F. Case 2: HER2 score for both the CNB specimen (E) and the surgically resected specimen (F) was 0. Immunoperoxidase reaction, original magnification ×200.

Figure 2

Cases with discordant judgment of HER2 score between CNB and surgically resected specimens. A-B. Case 54: HER2 score was 3+ for the CNB specimen (A) but 0 for the surgically resected specimen (B). The tumor had heterogeneous HER2 expression, and >30% of the area showed a strong membrane immunoreaction in the CNB specimen, whereas most of the area in the surgically resected specimen was HER2-negative. C-D. Case 84: HER2 score was 0 for the CNB specimen (C) but 2+ for the surgically resected specimen (D). This difference might have been due to suboptimal processing of CNB specimens or intratumor heterogeneity. E-F. Case 92: HER2 score was 2+ for the CNB specimen (E) but 3+ for the surgically resected specimen (F). Because the CNB specimen contained only a small amount of invasive component, the evaluation of HER2 was difficult. G-H. Case 94: HER2 score was 2+ for the CNB specimen (G) but 3+ for the surgically resected specimen (H). Processing of the CNB specimen might have been suboptimal, or the tumor may have been borderline in nature. Immunoperoxidase reaction, original magnification ×200.