HER2 作为指导 II 期结直肠癌辅助化疗的潜在生物标志物。
HER2 as a potential biomarker guiding adjuvant chemotherapy in stage II colorectal cancer.
机构信息
Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
出版信息
Eur J Surg Oncol. 2019 Feb;45(2):167-173. doi: 10.1016/j.ejso.2018.10.059. Epub 2018 Oct 19.
BACKGROUND
HER2 is a well-established therapeutic target in breast and gastric cancers, while the role of HER2 in colorectal cancer is unclear, and no studies have explored the impact of HER2 on the outcome of stage II colorectal cancer patients treated with 5-fluorouracial based adjuvant chemotherapy.
METHODS
We analyzed HER2 mRNA expression of 206 patients in GSE39582 dataset and explored the impact of HER2 expression on benefit from adjuvant chemotherapy for stage II colon cancer patients. We further validated the finding by retrospectively analyzing HER2 detection of immunohistochemistry in a cohort of 282 patients in Fudan University Shanghai Cancer Center (FUSCC).
RESULTS
In GSE39582 dataset, chemo-treated HER2-high patients had a better overall survival (OS) and relapse-free survival (RFS) versus chemo-naïve HER2-high patients (5-year OS: 100% vs 69.5%, 5-year RFS: 100% and vs 64%, P = 0.027 and 0.025, respectively). On the contrary, chemo-treated HER2-low patients had a worse RFS compared with chemo-naïve HER2-low patients (5-year RFS: 65.6% vs 82.1%, P = 0.022). In FUSCC cohort, chemo-treated HER2-positive patients exhibited better OS vs chemo-naïve HER2-positive patients (5-year OS: 100% vs 73.8%, P < 0.001), and showed marginal evidence of a lower probability of recurrence (5-year RFS: 74.4% vs 58.7%, P = 0.072). After stratifying by mismatch repair (MMR) status, the results only kept consistency in patients with pMMR status.
CONCLUSIONS
HER2-positve patients with stage II colorectal cancer can benefit from 5-fluorouracial based adjuvant chemotherapy, especially for patients with pMMR status.
背景
HER2 是乳腺癌和胃癌的一个成熟的治疗靶点，而 HER2 在结直肠癌中的作用尚不清楚，也没有研究探讨 HER2 对接受氟尿嘧啶为基础的辅助化疗的 II 期结直肠癌患者结局的影响。
方法
我们分析了 GSE39582 数据集 206 例患者的 HER2 mRNA 表达，并探讨了 HER2 表达对 II 期结肠癌患者接受辅助化疗获益的影响。我们通过回顾性分析复旦大学附属肿瘤医院（FUSCC）282 例患者的免疫组织化学 HER2 检测结果进一步验证了这一发现。
结果
在 GSE39582 数据集，与化疗初治 HER2 高表达患者相比，化疗后 HER2 高表达患者的总生存（OS）和无复发生存（RFS）更好（5 年 OS：100%比 69.5%，5 年 RFS：100%比 64%，P=0.027 和 0.025）。相反，化疗后 HER2 低表达患者的 RFS 较化疗初治 HER2 低表达患者差（5 年 RFS：65.6%比 82.1%，P=0.022）。在 FUSCC 队列中，化疗后 HER2 阳性患者的 OS 优于化疗初治 HER2 阳性患者（5 年 OS：100%比 73.8%，P<0.001），且复发的可能性更低（5 年 RFS：74.4%比 58.7%，P=0.072）。在错配修复（MMR）状态分层后，结果仅在 pMMR 状态患者中保持一致。
结论
HER2 阳性的 II 期结直肠癌患者可以从氟尿嘧啶为基础的辅助化疗中获益，特别是对于 pMMR 状态的患者。
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