Abstract: Brain metastases (BM) from colorectal cancer (CRC) are a rare but increasing event. Surgical resection of oligometastatic disease, including BM, may produce a survival benefit in selected patients. Previous studies described the HER-2 expression patterns in CRC patients, but its prognostic role still remains controversial. Information on the HER-2 expression in BM from CRC is currently lacking. Among the over 500 patients treated at our Department of Neurosurgery in the last 13 years (1999–2012), we identified a cohort of 50 consecutive CRC patients resected for BM. Clinical data were retrospectively reviewed using electronic hospital charts and surgical notes. Formalin-fixed, paraffin-embedded tissue samples were retrieved and histologically reviewed. HER-2 status was assessed on 4-μm sections by HerceptTest™, and scored by two pathologists according to gastric cancer HER-2 status guidelines. In score 2+ cases HER-2 gene copy number was analyzed by FISH, performed using the PathVysion HER-2 DNA Probe Kit. Median age at time of BM resection was 65 years (35–82); most patients were males (60%) with a good performance status. The majority of the BM were single (74%) and sited in the supratentorial area (64%); 2–4 lesions were diagnosed in 9 patients (18%), and >4 in 3 patients (6%). The rate of HER-2 positivity (defined as IHC score 3+ or IHC score 2+ and FISH gene amplification) was 8.1% for the primary CRC tumors and 12% for their corresponding BM. The concordance rate between primary tumors and matched BM was 89%. Median overall survival after neurosurgery was 6.5 months for HER-2 IHC score 0 vs. 4.6 months for HER-2 IHC score 1+/2+/3+; the difference was statistically significant (p = 0.01, Log-rank test). HER-2 positivity of our case cohort was low but comparable to literature. Concordance rate of HER-2 expression between BM and corresponding primary tumors is high and similar to those reported for breast and gastric cancers. Our data suggest a potential negative prognostic value of HER-2 expression in brain lesions from CRC.
Keywords: colorectal cancer; brain metastases; neurosurgery; HER-2; survival
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Aprile, G.; De Maglio, G.; Menis, J.; Casagrande, M.; Tuniz, F.; Pisa, E.F.; Fontanella, C.; Skrap, M.; Beltrami, A.C.; Fasola, G.; Pizzolitto, S. HER-2 Expression in Brain Metastases from Colorectal Cancer and Corresponding Primary Tumors: A Case Cohort Series. Int. J. Mol. Sci. 2013, 14, 2370-2387.
Aprile G, De Maglio G, Menis J, Casagrande M, Tuniz F, Pisa EF, Fontanella C, Skrap M, Beltrami AC, Fasola G, Pizzolitto S. HER-2 Expression in Brain Metastases from Colorectal Cancer and Corresponding Primary Tumors: A Case Cohort Series. International Journal of Molecular Sciences. 2013; 14(2):2370-2387.
Aprile, Giuseppe; De Maglio, Giovanna; Menis, Jessica; Casagrande, Mariaelena; Tuniz, Francesco; Pisa, Edith F.; Fontanella, Caterina; Skrap, Miran; Beltrami, Alberto C.; Fasola, Gianpiero; Pizzolitto, Stefano. 2013. "HER-2 Expression in Brain Metastases from Colorectal Cancer and Corresponding Primary Tumors: A Case Cohort Series." Int. J. Mol. Sci. 14, no. 2: 2370-2387.