HER2 gene (ERBB2) amplification is a low-frequency driver with potential predictive value in gallbladder carcinoma
HER2 gene (ERBB2) amplification is a low-frequency driver with potential predictive value in gallbladder carcinoma
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DOI：
10.1007/s00428-019-02706-6
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发表时间：
2020-06-01
期刊：
影响因子：
3.5
通讯作者：
Goeppert, Benjamin
中科院分区：
文献类型：
--
作者：
Albrecht, Thomas;Rausch, Melina;Goeppert, Benjamin
胆囊癌（GBC）是一种侵袭性的癌症，预后很差。最近的病例报告强调了人表皮生长因子受体2（HER 2）作为胆道癌个体化治疗的一个有希望的靶点;然而，目前关于GBC中HER 2阳性的数据是矛盾的。本研究旨在评估HER 2阳性的比例及其在一个大型且特征良好的欧洲GBC队列中的临床意义。根据免疫组织化学和双色显色原位杂交检测胃癌HER 2的最新共识，在186例手术切除的胆囊腺癌和一个共存的高级别胆管上皮内瘤变（BilIN，n = 74）的子集中确定HER 2状态。在所有病例的5.4%（n = 10）中观察到HER 2阳性。在伴随高级别BilIN的患者中，四个阳性样本中的两个也在前体病变中显示扩增，而在剩下的两个病例中，阳性仅限于浸润性肿瘤或高级别BilIN。11例病例中发现的可疑染色并未伴有基因扩增。HER 2阳性组的分期与HER 2阴性组显著不同，大多数病例出现在IV期，但生存率有下降的趋势。1例接受双重HER 2抑制的患者几乎达到完全临床缓解，尽管在转移状态下开始治疗。我们的研究结果揭示了HER 2阳性的低患病率，并强调HER 2基因扩增是胆囊癌发生的早期潜在驱动事件。需要前瞻性标准化HER 2检测和随机对照研究来证明靶向HER 2抑制在GBC中的临床疗效。
Gallbladder carcinoma (GBC) is an aggressive type of cancer with a dismal prognosis. Recent case reports have highlighted the human epidermal growth factor receptor 2 (HER2) as a promising target for individualized therapy in biliary tract cancer; however, current data on HER2 positivity in GBC is contradictory. This study aimed to assess the proportion of HER2 positivity and its clinical implications in a large and well-characterized European GBC cohort. HER2 status was determined in 186 cases of surgically resected gallbladder adenocarcinoma and a subset of coexistent high-grade biliary intraepithelial neoplasia (BilIN, n = 74) in accordance with the up-to-date consensus for HER2 testing in gastric cancer by immunohistochemistry and dual-color chromogenic in situ hybridization. Positivity for HER2 was observed in 5.4% of all cases (n = 10). In those patients with concomitant high-grade BilIN, two of four positive samples also showed amplification in the precursor lesion, while in the two remaining cases, positivity was either confined to invasive tumor or high-grade BilIN, exclusively. Equivocal staining found in eleven cases was not accompanied by gene amplification. Staging of the HER2-positive group was significantly different from the HER2-negative group with most cases presenting at stage IV, paralleled by a trend towards decreased survival. One patient who received dual HER2 inhibition almost went into full clinical remission despite treatment initiation in a metastasized state. Our results reveal a low prevalence of HER2 positivity and highlight HER2 gene amplification as an early, potentially driving event in gallbladder carcinogenesis. Prospective standardized HER2 testing and randomized control studies are needed to prove clinical efficacy of targeted HER2 inhibition in GBC.