Department of Oncology, University and General Hospital, 33100 Udine, Italy.
Int J Mol Sci. 2013 Jan 24;14(2):2370-87. doi: 10.3390/ijms14022370.
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.
脑转移瘤（BM）来自结直肠癌（CRC）是一种罕见但日益增加的事件。包括 BM 在内的寡转移瘤的手术切除可能会给某些患者带来生存获益。先前的研究描述了 CRC 患者的 HER-2 表达模式，但它的预后作用仍存在争议。目前关于 CRC 脑转移瘤中 HER-2 表达的信息尚缺乏。在过去 13 年（1999-2012 年）我科神经外科治疗的 500 多名患者中，我们确定了一组连续的 50 例 CRC 患者，这些患者因 BM 而接受手术切除。使用电子病历和手术记录回顾临床数据。检索福尔马林固定、石蜡包埋的组织样本，并进行组织学检查。使用 HerceptTest™，通过 4-μm 切片评估 HER-2 状态，并由两名病理学家根据胃癌 HER-2 状态指南进行评分。在评分 2+的病例中，通过 FISH 分析 HER-2 基因拷贝数，使用 PathVysion HER-2 DNA Probe Kit 进行分析。BM 切除时的中位年龄为 65 岁（35-82 岁）；大多数患者为男性（60%），表现状态良好。大多数 BM 为单发（74%），位于幕上区域（64%）；9 例患者（18%）诊断为 2-4 个病变，3 例患者（6%）诊断为>4 个病变。原发性 CRC 肿瘤的 HER-2 阳性率（定义为 IHC 评分 3+或 IHC 评分 2+且 FISH 基因扩增）为 8.1%，相应 BM 的阳性率为 12%。原发性肿瘤与匹配 BM 的一致性率为 89%。神经外科手术后的中位总生存期为 HER-2 IHC 评分 0 的 6.5 个月与 HER-2 IHC 评分 1+/2+/3+的 4.6 个月；差异具有统计学意义（p=0.01，Log-rank 检验）。我们的病例组 HER-2 阳性率较低，但与文献相似。BM 与相应原发性肿瘤之间 HER-2 表达的一致性率较高，与乳腺癌和胃癌的报道相似。我们的数据表明，CRC 脑转移瘤中 HER-2 表达可能具有潜在的负预后价值。
