Tominaga Naoyuki, Gotoda Takuji, Hara Megumi, Hale Matthew D, Tsuchiya Takayoshi, Matsubayashi Jun, Kono Shin, Kusano Chika, Itoi Takao, Fujimoto Kazuma, Moriyasu Fuminori, Grabsch Heike I
Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan.
Departments of Internal Medicine and Gastrointestinal Endoscopy, Saga Medical School, Saga, Japan.
Gastric Cancer. 2016 Apr;19(2):553-560. doi: 10.1007/s10120-015-0502-3. Epub 2015 May 19.
National guidelines recommend trastuzumab for treatment of patients with metastatic HER2-positive gastric cancer (GC). There is currently no guideline indicating the number of biopsy specimens and the location from which they should be obtained to reliably determine the human epidermal growth factor receptor 2 (HER2) status in GC. The aim of this pilot study was (a) to quantify HER2-positive tumor cells in different tumor regions to assess the spatial heterogeneity of HER2 expression and (b) to establish the required number of biopsy specimens and the location from which they should be obtained within the tumor to achieve concordance between HER2 expression status in the biopsy specimens and the resection specimen.
HER2 expression was quantified in six different regions of 24 HER2-positive GC and in six virtual biopsy specimens from different luminal regions. Intratumoral regional heterogeneity and concordance between HER2 status in the biopsy specimens and the resection specimen were analyzed.
HER2-positive cells were more frequent in the luminal tumor surface compared with deeper layers (p < 0.001). GCs with differentiated histological features were more commonly HER2 positive (p < 0.001). Assessment of HER2 expression status in five biopsy specimens was sufficient to achieve 100 % concordance between the biopsy specimens and the resection specimen.
This is the first study to suggest preferential HER2 positivity at the luminal surface in GC and to establish a minimum number of biopsy specimens needed to obtain a biopsy HER2 result which is identical to that from the whole tumor. Our study suggests that HER2 testing in five tumor-containing endoscopic biopsy specimens from the proximal (oral) part of the tumor is advisable. The results from this pilot study require validation in a prospective study.
国家指南推荐使用曲妥珠单抗治疗转移性HER2阳性胃癌（GC）患者。目前尚无指南指明为可靠确定GC患者的人表皮生长因子受体2（HER2）状态应获取的活检标本数量及取材部位。本初步研究的目的是：（a）量化不同肿瘤区域的HER2阳性肿瘤细胞，以评估HER2表达的空间异质性；（b）确定活检标本所需数量及在肿瘤内的取材部位，以使活检标本与切除标本的HER2表达状态达成一致。
对24例HER2阳性GC的六个不同区域以及来自不同管腔区域的六个虚拟活检标本中的HER2表达进行量化。分析肿瘤内区域异质性以及活检标本与切除标本中HER2状态的一致性。
与深层相比，管腔内肿瘤表面的HER2阳性细胞更为常见（p < 0.001）。具有分化组织学特征的GC更常为HER2阳性（p < 0.001）。评估五个活检标本中的HER2表达状态足以使活检标本与切除标本达成100%的一致性。
这是第一项表明GC管腔表面HER2优先阳性并确定获得与整个肿瘤相同的活检HER2结果所需的最少活检标本数量的研究。我们的研究表明，可取肿瘤近端（口侧）含肿瘤的五个内镜活检标本进行HER2检测。本初步研究的结果需要在前瞻性研究中进行验证。
