Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehang-ro, Jongno-gu, Seoul 110-744, Republic of Korea.
Cancer Chemother Pharmacol. 2013 Jun;71(6):1435-43. doi: 10.1007/s00280-013-2141-x. Epub 2013 Apr 30.
We aimed to investigate the role of BRCA1 nuclear expression in sporadic gastric cancer; currently, the role remains unknown.
Patients with gastric cancer who received curative operation with D2 dissection were enrolled in this study. Adjuvant chemotherapy was administered at the discretion of the physician. According to BRCA1 nuclear expression analysis by immunohistochemistry (IHC) on tissue microarrays using anti-BRCA1 antibody MS110, BRCA1 expression was classified as negative, low expression, and high expression.
Among 318 cases, 155 cases (48.7 %) were identified as BRCA1-negative by IHC and 96 cases (30.2 %) revealed BRCA1 low expression, 67 cases (21.0 %) showed BRCA1 high expression. The negative or reduced expression of BRCA1 was more frequent in more advanced-stage disease (p < 0.001) and was associated with perineural invasion (p = 0.032). Disease-free survival (DFS) was significantly decreased with reduced BRCA1 expression (p = 0.027). This tendency was also observed in overall survival (OS), although the difference was not significant. The poorer prognosis of BRCA1-negative tumors was overcome through adjuvant chemotherapy. The benefit of adjuvant chemotherapy for DFS and OS in stage III was enhanced only in BRCA1-negative tumors (p < 0.001, p < 0.001, respectively), but not in BRCA1-positive tumors (p = 0.236, p = 0.148, respectively).
The reduction of BRCA1 nuclear expression is associated with advanced stage and perineural invasion. Moreover, negative BRCA1 nuclear expression is a predictive marker regarding the benefit of adjuvant chemotherapy in sporadic gastric cancer; these novel findings are of great importance, and further, larger studies are warranted.
我们旨在研究 BRCA1 核表达在散发性胃癌中的作用；目前，其作用尚不清楚。
本研究纳入了接受 D2 清扫术根治性手术的胃癌患者。辅助化疗由医生决定。根据组织微阵列免疫组化（IHC）用抗 BRCA1 抗体 MS110 对 BRCA1 核表达进行分析，将 BRCA1 表达分为阴性、低表达和高表达。
在 318 例病例中，155 例（48.7%）的 IHC 结果为 BRCA1 阴性，96 例（30.2%）为 BRCA1 低表达，67 例（21.0%）为 BRCA1 高表达。BRCA1 的阴性或低表达在较晚期疾病中更为常见（p < 0.001），与神经周围侵犯有关（p = 0.032）。BRCA1 表达降低与无病生存期（DFS）降低显著相关（p = 0.027）。这种趋势在总生存期（OS）中也观察到，尽管差异无统计学意义。BRCA1 阴性肿瘤的不良预后通过辅助化疗得到改善。辅助化疗对 III 期患者的 DFS 和 OS 的获益仅在 BRCA1 阴性肿瘤中增强（p < 0.001，p < 0.001），而在 BRCA1 阳性肿瘤中没有增强（p = 0.236，p = 0.148）。
BRCA1 核表达减少与晚期和神经周围侵犯有关。此外，BRCA1 核阴性表达是散发性胃癌辅助化疗获益的预测标志物；这些新发现意义重大，需要进一步开展更大规模的研究。
