Kurokawa Yukinori, Matsuura Nariaki, Kawabata Ryohei, Nishikawa Kazuhiro, Ebisui Chikara, Yokoyama Yuhki, Shaker Mohammed Nouri, Hamakawa Takuya, Takahashi Tsuyoshi, Takiguchi Shuji, Mori Masaki, Doki Yuichiro
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan,
Ann Surg Oncol. 2014 Dec;21 Suppl 4:S584-90. doi: 10.1245/s10434-014-3690-x. Epub 2014 Apr 18.
Various kinds of molecular targeted drugs to inhibit receptor tyrosine kinases (RTKs) have been recently developed. The relationship between the expression status of major RTKs and prognosis in gastric cancer remains unclear. We conducted a multicenter study to evaluate the prognostic impact of the expression of epidermal growth factor receptor (EGFR), c-Met, platelet-derived growth factor receptor (PDGFR), and c-Kit in gastric cancer.
This study included 153 gastric cancer patients who underwent gastrectomy at 9 institutions between 2000 and 2006. Expression status of EGFR, c-Met, PDGFR, and c-Kit were evaluated with immunohistochemistry (IHC) centrally. Overall survival based on RTK expression status was statistically compared. Cox multivariate analysis was conducted to adjust for potentially confounding factors.
The positive rates for EGFR, c-Met, PDGFR, and c-Kit were 14.4, 24.8, 41.2, and 11.1 %, respectively. Significant interactions with expression status were observed for pathological N stage with EGFR; HER2-status with c-Met; tumor location, histology, and pathological N stage with PDGFR; and no examined variables with c-Kit. Concomitant HER2 positivity was observed for 0.7 % of tumors positive for EGFR, 3.9 % for c-Met, 4.6 % for PDGFR, and 1.3 % for c-Kit. There were some differences in overall survival between patients with or without RTK expression, but only c-Kit expression showed a significant survival difference in Cox multivariate analysis (P = 0.046).
Our multicenter study indicated that IHC expression of 4 RTKs had some prognostic impact and that c-Kit-positive status may be a significant indicator of good prognosis in gastric cancer patients.
近年来已研发出多种抑制受体酪氨酸激酶（RTK）的分子靶向药物。胃癌中主要RTK的表达状态与预后之间的关系仍不清楚。我们开展了一项多中心研究，以评估表皮生长因子受体（EGFR）、c-Met、血小板衍生生长因子受体（PDGFR）和c-Kit在胃癌中的表达对预后的影响。
本研究纳入了2000年至2006年间在9家机构接受胃切除术的153例胃癌患者。集中采用免疫组织化学（IHC）评估EGFR、c-Met、PDGFR和c-Kit的表达状态。基于RTK表达状态的总生存期进行了统计学比较。进行Cox多因素分析以调整潜在的混杂因素。
EGFR、c-Met、PDGFR和c-Kit的阳性率分别为14.4%、24.8%、41.2%和11.1%。观察到EGFR与病理N分期、c-Met与HER2状态、PDGFR与肿瘤位置、组织学及病理N分期之间存在显著的表达状态相互作用；而c-Kit与所检测变量之间无此情况。EGFR阳性肿瘤中0.7%同时伴有HER2阳性，c-Met阳性肿瘤中为3.9%，PDGFR阳性肿瘤中为4.6%，c-Kit阳性肿瘤中为1.3%。RTK表达阳性和阴性的患者之间总生存期存在一些差异，但在Cox多因素分析中只有c-Kit表达显示出显著的生存差异（P = 0.046）。
我们的多中心研究表明，4种RTK的IHC表达具有一定的预后影响，c-Kit阳性状态可能是胃癌患者预后良好的一个重要指标。
