Matsumoto Tomohiro, Sasako Mitsuru, Mizusawa Junki, Hirota Seiichi, Ochiai Atsushi, Kushima Ryoji, Katai Hitoshi, Tanaka Yoichi, Fukushima Norimasa, Nashimoto Atsushi, Tsuburaya Akira
Department of Upper Gastrointestinal Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
Gastric Cancer. 2015 Jul;18(3):467-75. doi: 10.1007/s10120-014-0398-3. Epub 2014 Jul 4.
Human epidermal growth factor receptor 2 (HER2) is likely overexpressed and/or amplified in locally advanced gastric cancer with extensive (bulky N2 or paraaortic) lymph node metastasis, and patients may benefit from treatment with anti-HER2 antibodies. This study evaluated the frequency of HER2 overexpression and amplification in The Japanese Gastric Cancer Association (JGCA)-N3 and JGCA-bulky N2 tumors and the correlation between HER2 status and survival.
HER2 status was assessed using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in tumor tissue samples from 89 patients with gastric adenocarcinoma enrolled in the phase II JCOG0001 and JCOG0405 trials. HER2 positivity was defined as IHC3+ or IHC2+ with confirmatory FISH results.
Of the 89 tumor samples, 24 (27 %) showed HER2 positivity, including 16 scored as IHC3+ and 8 as IHC2+ and FISH positive. Multivariate analysis showed that the HER2 positivity rate was significantly higher in evaluable differentiated tumors than in undifferentiated tumors [18/44 (40.9 %) vs. 5/42 (11.9 %)]. Although the apparent OS curve of HER2 positive was superior to that of HER2 negative patients, HER2 status was not a statistically significant prognostic factor in multivariate analysis.
The HER2 positivity rate was relatively high in patients with JGCA-bulky N2 and JGCA-N3 gastric adenocarcinoma, suggesting that HER2 evaluation is essential to select the therapeutic regimen for neoadjuvant chemotherapy for this group of patients.
人表皮生长因子受体2（HER2）可能在伴有广泛（巨大N2或腹主动脉旁）淋巴结转移的局部晚期胃癌中过表达和/或扩增，患者可能从抗HER2抗体治疗中获益。本研究评估了日本胃癌协会（JGCA）-N3和JGCA-巨大N2肿瘤中HER2过表达和扩增的频率以及HER2状态与生存之间的相关性。
在参加II期JCOG0001和JCOG0405试验的89例胃腺癌患者的肿瘤组织样本中，使用免疫组织化学（IHC）和荧光原位杂交（FISH）评估HER2状态。HER2阳性定义为IHC3+或IHC2+且FISH结果证实。
在89个肿瘤样本中，24个（27%）显示HER2阳性，包括16个评分为IHC3+和8个为IHC2+且FISH阳性。多变量分析显示，可评估的分化型肿瘤中的HER2阳性率显著高于未分化肿瘤[18/44（40.9%）对5/42（11.9%）]。虽然HER2阳性患者的表观总生存曲线优于HER2阴性患者，但在多变量分析中HER2状态不是具有统计学意义的预后因素。
JGCA-巨大N2和JGCA-N3胃腺癌患者的HER2阳性率相对较高，提示HER2评估对于选择该组患者新辅助化疗的治疗方案至关重要。
