Analysis of clinical findings and identification of molecular genetic aberrations in the tumor cells will be able to elaborate an individual approach to treating patients with glioblastoma in order to increase their survival rates and to improve quality of life.

Background: Her-2-neu is one of the major genes and proteins, whose amplification and expression is widely used in modern medical practice in patients with breast carcinoma (BC). . This is a marker of poor prognosis and the "target" for Herceptin. The role of this marker in brain metastases is not very well investigated as it is in a primary tumor. Aim: To investigate the incidence of molecular variants of breast carcinoma in brain metastases (BM), to analyze Her-2-neu presence in them and evaluate its prognostic significance in patients with BMBC. Patients and methods: 90 FFPE tumor tissues and clinical data from consented patients with BMBC treated with surgery at the NN Burdenko Neurosurgery Institute (median age 52, age range 29-73 years) and 71 FFPE tumor tissues and clinical data from consented patients with primary BC without BM treated with surgery in AI Burnacyan Institute (median age 58, age range 28-80 years) have been obtained and evaluated. IHC staining of all 161 cases was performed with monoclonal antibodies to ER, PR, Ki-67and Her-2-neu (DAKO); Fluorescence in situ hybridization Her-2-neu LSI and CEP17 was also performed . Her-2 neu expression and amplification were estimated according to the standard ASCO recommendations. A special questionnaire was completed in order to obtain information about outcome of the patients. Statistical analysis was performed using the STATISTICA 8.0 software. Results: There were 5 molecular variants in BC and BMBC groups according to the ER, PR, Ki-67 and Her-2-Neu IHC expression and Her-2-Neu amplification. Their incidence among two groups were: luminal A - 42% vs. 9%, luminal B -10% vs. 3%, luminal Her-2-Neu positive - 14% vs. 27%, classical her-2-Neu positive -21% vs. 22%, and triple negative -13% vs. 27%, correspondingly. Patients in the BM group were in average 6 years younger than patients in ‘pure’ BC group. In BMBC group median time of BM's development among Her-2-Neu (amplified Her-2-neu gene) patients was significantly shorter than that among Her-2-neu -negative (without amplification) patients: 40 months (range 8-288) versus 84 months (range 24-131 (p<0,05). The general survival time from first signs of BM was 8 months (ranges 0-89) in Her-2-neu- positive patients versus 13 months (ranges 0-72) in Her-2-neu -negative patients. Conclusions: Despite the fact that luminal A variant of BC is the most common one among primary tumors, in patients with BMBC triple negative and luminal Her-2-neu variants occurred more frequently. As age analysis showed, patients from BMBC group were younger than patients without BM. Therefore we believe that ‘brain metastatic’ carcinomas occur in a much younger population. Patients with BMBC Her-2-neu amplification have more aggressive development of disease and shorter survival time, than without Her-2-neu amplification. Citation Format: Daniil Rotin, Oxana Paklina, NV Lobanova, GL Kobyakov, Olga Potapova. Incidence of molecular variants with and without Her-2-Neu expression and amplification in brain metastases of breast carcinoma and its prognostic significance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5127. doi:10.1158/1538-7445.AM2013-5127