Yagisawa Masataka, Sawada Kentaro, Nakamura Yoshiaki, Fujii Satoshi, Yuki Satoshi, Komatsu Yoshito, Yoshino Takayuki, Sakamoto Naoya, Taniguchi Hiroya
Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan; Department of Medical Oncology, Japanese Red Cross Kitami Hospital, Kitami, Hokkaido, Japan.
Department of Medical Oncology, Kushiro Rosai Hospital, Kushiro, Hokkaido, Japan.
Clin Colorectal Cancer. 2021 Jun;20(2):113-120.e1. doi: 10.1016/j.clcc.2020.11.002. Epub 2020 Nov 13.
The prognostic value and molecular landscape of human epidermal growth factor receptor 2 (HER2) low-expressing (HER2-L) metastatic colorectal cancer (mCRC) remain unclear.
This study enrolled patients with mCRC who had undergone surgical resection of primary tumor. Using the specimen, we evaluated HER2 expression by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). HER2 positivity was defined as follows: HER2 positivity (HER2-Pos) as IHC 3 + or IHC 2+/FISH positive, HER2-L as IHC 2+/FISH negative or IHC 1+, and HER2 negativity (HER2-Neg) as IHC 0+. Gene alterations were determined by next-generation sequencing.
Between 2005 and 2015, a total of 370 patients were analyzed, comprising 15 patients (4%) with HER2-Pos, 21 (6%) with HER2-L, and 334 (90%) with HER2-Neg disease. The clinicopathologic characteristics among groups had no differences. HER2-L had a significantly higher proportion of coaltered RAS mutation than HER2-Pos (P = .037). With a median follow-up of 101.8 months, HER2-L had a significantly better median overall survival than HER2-Pos (P = .029) (18.2 months in HER2-Pos vs. 33.3 in HER2-L vs. 27.9 in HER2-Neg). In 58 patients harboring wild-type RAS and receiving anti-EGFR antibody therapy, HER2-L had a better median progression-free survival tendency than HER2-Pos, with 2.2 months in HER2-Pos, 7.8 in HER2-L, and 5.1 in HER2-Neg (P = .036).
HER2-L mCRC showed a better prognosis than HER2-Pos mCRC, and it is similar to HER2-Neg mCRC. Hence, HER2-L mCRC might have different biologic behavior in terms of prognostic value and molecular landscape of mCRC, suggesting the possibility of implementation of HER2-guided clinical development against HER2-expressing mCRC.
人表皮生长因子受体2（HER2）低表达（HER2-L）转移性结直肠癌（mCRC）的预后价值和分子特征仍不清楚。
本研究纳入了接受原发性肿瘤手术切除的mCRC患者。利用标本，我们通过免疫组织化学（IHC）和荧光原位杂交（FISH）评估HER2表达。HER2阳性定义如下：HER2阳性（HER2-Pos）为IHC 3+或IHC 2+/FISH阳性，HER2-L为IHC 2+/FISH阴性或IHC 1+，HER2阴性（HER2-Neg）为IHC 0+。通过下一代测序确定基因改变。
2005年至2015年期间，共分析了370例患者，其中15例（4%）为HER2-Pos，21例（6%）为HER2-L，334例（90%）为HER2-Neg疾病。各组间的临床病理特征无差异。HER2-L中RAS共突变的比例显著高于HER2-Pos（P = 0.037）。中位随访101.8个月，HER2-L的中位总生存期显著优于HER2-Pos（P = 0.029）（HER2-Pos为18.2个月，HER2-L为33.3个月，HER2-Neg为27.9个月）。在58例携带野生型RAS并接受抗EGFR抗体治疗的患者中，HER2-L的中位无进展生存期趋势优于HER2-Pos，HER2-Pos为2.2个月，HER2-L为7.8个月，HER2-Neg为5.1个月（P = 0.036）。
HER2-L mCRC的预后优于HER2-Pos mCRC，且与HER2-Neg mCRC相似。因此，HER2-L mCRC在mCRC的预后价值和分子特征方面可能具有不同的生物学行为，提示针对HER2表达的mCRC实施HER2指导的临床开发的可能性。
