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Her-2/neu status in breast cancer metastases to the central nervous system
Kelly C Lear-Kaul1, Hye-Ryoung Yoon, Bette K Kleinschmidt-DeMasters
1Department of Pathology, University of Colorado Health Sciences Center, Denver 80262, USA.
Context:
Breast cancer is lethal when it metastasizes; one frequent site for spread is the central nervous system (CNS). Approximately 15% to 30% of breast cancers overexpress the protein HER-2/neu at the primary site, but there are few data on whether metastases from these tumors overexpress HER-2/neu and might be responsive to the potentially toxic anti-HER-2/neu immunotherapy (trastuzumab [Herceptin]) used in patients with disseminated disease.
Objective:
To assess CNS breast cancer metastases for HER-2/neu protein overexpression by immunohistochemistry and gene amplification by fluorescence in situ hybridization (FISH) and to compare the status in primary and metastatic sites in the same patient, whenever possible.
Design:
Central nervous system breast cancer metastases (n = 53) from 33 patients and corresponding primary breast cancer specimens in a subset of these patients (n = 12) were retrospectively identified in surgical pathology and autopsy databases. Fluorescence in situ hybridization analysis using PathVysion probes for HER-2/neu and chromosome enumeration probe 17 (CEP 17) and immunohistochemistry using the c-Erb-B2 antibody (Dako A0485) were compared. Immunohistochemical sections were evaluated by both visual and image analysis techniques.
Results:
Of 31 cases assessable by FISH, 26% showed gene amplification. One hundred percent concordance for HER-2/neu status was detected between the primary and CNS metastatic lesions in 10 of 10 patients analyzed by FISH; lesser concordance was noted in 12 cases compared by immunohistochemistry. In 9 patients with multiple CNS metastases, FISH showed concordance among different lesions within the same patient.
Conclusions:
When FISH is the detection method, CNS metastases accurately reflect the HER-2/neu status of the primary tumor. Central nervous system metastases from breast cancer received as surgical specimens can therefore be used to assess HER-2/neu status in patients in whom the primary tumor is unavailable for analysis.
Insights
Central nervous system (CNS) breast cancer metastases accurately reflect HER-2/neu status when assessed by fluorescence in situ hybridization (FISH). This allows for reliable HER-2/neu testing on metastatic sites when primary tumors are unavailable.
Area of Science:
- Oncology
- Molecular Pathology
Background:
- Breast cancer metastasis to the central nervous system (CNS) is a significant cause of mortality.
- HER-2/neu overexpression occurs in 15-30% of primary breast cancers, but its status in CNS metastases is not well-characterized.
- Accurate HER-2/neu assessment is crucial for guiding anti-HER-2/neu immunotherapy (trastuzumab) in patients with advanced disease.
Purpose of the Study:
- To evaluate HER-2/neu protein overexpression and gene amplification in CNS breast cancer metastases.
- To compare HER-2/neu status between primary breast tumors and their corresponding CNS metastases.
- To determine the reliability of CNS metastases as a surrogate for primary tumor HER-2/neu status.
Main Methods:
- Retrospective analysis of 53 CNS breast cancer metastases and 12 corresponding primary tumors.
- Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were used to assess HER-2/neu status.
- Comparison of IHC and FISH results, including visual and image analysis for IHC.
Main Results:
- FISH analysis revealed HER-2/neu gene amplification in 26% of assessable CNS metastases.
- 100% concordance in HER-2/neu status between primary tumors and CNS metastases was observed when using FISH (10/10 patients).
- FISH demonstrated consistent HER-2/neu status across multiple CNS lesions within the same patient (9 patients).
Conclusions:
- CNS metastases accurately reflect the HER-2/neu status of the primary breast tumor when assessed by FISH.
- Surgically resected CNS metastases can serve as a reliable source for HER-2/neu testing when primary tumors are unavailable.
- FISH is the preferred method for assessing HER-2/neu status in CNS metastases due to high concordance with primary tumors.
