HER-2 Expression in Brain Metastases from Colorectal Cancer and Corresponding Primary Tumors: A Case Cohort Series

Jessica Menis,Alberto Beltrami,Giuseppe Aprile,Gianpiero Fasola,Francesco Tuniz,Caterina Fontanella,Giovanna De Maglio,Stefano Pizzolitto,Mariaelena Casagrande,Edith Pisa,Miran Skrap

doi:10.3390/ijms14022370

Jessica Menis, Alberto Beltrami + Show 9 more

Open Access

https://doi.org/10.3390/ijms14022370

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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.

Highlights

Brain metastases (BM) from colorectal cancer (CRC) are a rare but increasing event, reported to occur in less than 5% of patients at the time of diagnosis and in up to 10% within the course of treatment [1]
We described the expression of HER-2 in cerebral metastases, gathering clinical and pathological data from 50 CRC patients who underwent neurosurgery in the past 13 years (1999–2012)
Seventy-four percent of the primary tumors were resected: in 19 patients the tumor was located in the colon, with 17 patients it was in the rectum, while a clear distinction was not possible in 14 cases (Table 1)

Summary

Introduction

Brain metastases (BM) from colorectal cancer (CRC) are a rare but increasing event, reported to occur in less than 5% of patients at the time of diagnosis and in up to 10% within the course of treatment [1]. Their incidence is expected to rise as a consequence of the improved survival reported for patients with metastatic CRC, that reflects the increased number of available medical treatments [2] and the significant progress in surgical techniques [3]. Other favorable prognostic factors include younger age (

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