Abstract

Abstract Introduction: Breast carcinoma is the second common type of cancer metastasizing into the brain. Although the frequency of Her-2 positive primary breast tumors is no more than 30%, a higher occurrence of brain metastases has been reported for patients with positive Her-2/neu primary tumors. We investigated here expression of Her-2 protein and amplification of Her-2 gene in brain metastasis tissues of breast carcinoma patients. Patients and Methods: FFPE tumor tissues were obtained from consented patients treated with surgery at the NN Burdenko Neurosurgery Institute in 2004–2007. Total of 42 cases of brain metastases (BM) with breast tissue origin were evaluated. Solitary BM occurred in 59% (16/27) patients, while multiple metastatic lesions were observed in 41% (11/27) patients. The median age was 53 (range 29 − 73 years). Her-2/neu gene amplification was analyzed by fluorescent in situ hybridization (FISH). Levels of protein expression were detected by immunohistochemistry (IHC) according to the DAKO HercepTest grading system. Membranous staining intensiveness was estimated by a semi-quantitative method (from 0 to 3+). Cases with Her-2 IHC expression score of 2+ were reconfirmed by FISH analysis. Statistical analysis was done using STATISTICA 6.0 software. Results: Over-expression of Her-2 protein was observed in 50% (21/42) cases, while only in 7% (3/42) cases level of HER-2 protein was graded as negative (scores 0 and 1+). In 43% (18/42) cases IHC score was scored as 2+, and for those cases HER-2/neu gene amplification was performed using FISH analysis. Amplification of Her-2/neu was detected in 72% (13/18) cases in that group. Over-expression of Her-2/neu was similar in tissues from patients with a single metastatic lesion (63% (10/16) cases) compared to that of patients with multiple brain metastases (60% (25/42) of cases). Conclusions: Despite relatively lower incidence in primary tumors, Her-2/neu positive breast cancer tumors prevail in breast cancer brain metastases (about 60%), perhaps attributing to the higher malignant potential of such tumors. We found no difference in Her-2/neu protein expression levels in patients with single and multiple brain metastases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C41.

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