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HER-2 Expression in Brain Metastases from Colorectal Cancer and Corresponding Primary Tumors: A Case Cohort Series
Department of Oncology, University and General Hospital, 33100 Udine, Italy
Department of Pathology, University and General Hospital, 33100 Udine, Italy
Department of Neurosurgery, University and General Hospital, 33100 Udine, Italy
Institute of Hygiene and Epidemiology, University and General Hospital, 33100 Udine, Italy
Institute of Pathology, University and General Hospital, 33100 Udine, Italy
* Author to whom correspondence should be addressed.
Received: 5 November 2012; in revised form: 9 January 2013 / Accepted: 12 January 2013 / Published: 24 January 2013
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.