De Stefano Alfonso, Rosanova Mario, Malapelle Umberto, Martini Maurizio, De Falco Stefano, Attademo Laura, Fiore Giovanni, Cenci Tonia, Bellevicine Claudio, De Placido Sabino, Troncone Giancarlo, Carlomagno Chiara
Department of Clinical Medicine and Surgery, Federico II University, Naples - Italy.
Department of Public Health, Federico II University, Naples - Italy.
Int J Biol Markers. 2017 Oct 31;32(4):e474-e477. doi: 10.5301/ijbm.5000273.
Analysis of K- and N-RAS mutations is mandatory before planning treatment of metastatic colorectal cancer, because only RAS wild-type (WT) patients can benefit from treatment with anti-EGFR monoclonal antibodies (cetuximab and panitumumab).
Here we report the case of a 69-year-old male patient affected by metastatic sigmoid cancer. He underwent left hemicolectomy, and histology diagnosed a well-differentiated, pT4, node-positive adenocarcinoma; KRAS analysis performed with direct sequencing identified a mutation in exon 2 of the KRAS gene (GGT->GTT). After first-line chemotherapy with FOLFOX6 plus bevacizumab, the patient underwent surgical resection of residual liver metastases. Histology showed metastatic deposits from colic adenocarcinoma with extensive coagulative necrosis. Mutational analysis of the KRAS gene was also performed on liver metastases by pyrosequencing assay, and no mutation was identified. Due to the discordant results (GGT->GTT exon 2 KRAS mutation in the primary tumor, and KRAS-WT in the liver metastases), mutational analysis on liver metastasis was repeated using next-generation sequencing and enriching the sample in tumor cells by manual microdissection; the same type of mutation of the primary tumor (GGT->GTT exon 2 KRAS gene) was confirmed.
Accurate tissue sampling and adequately sensitive assays are essential to correctly identify colorectal cancer patients who can be treated with an anti-EGFR monoclonal antibody.
在计划治疗转移性结直肠癌之前，必须对K-RAS和N-RAS突变进行分析，因为只有RAS野生型（WT）患者才能从抗表皮生长因子受体（EGFR）单克隆抗体（西妥昔单抗和帕尼单抗）治疗中获益。
在此我们报告一例69岁男性转移性乙状结肠癌患者。他接受了左半结肠切除术，组织学诊断为高分化、pT4、淋巴结阳性腺癌；采用直接测序法进行的KRAS分析确定KRAS基因外显子2存在突变（GGT->GTT）。在接受FOLFOX6联合贝伐单抗一线化疗后，患者接受了残余肝转移灶的手术切除。组织学显示为结肠腺癌转移灶，伴有广泛的凝固性坏死。还通过焦磷酸测序法对肝转移灶进行了KRAS基因突变分析，未发现突变。由于结果不一致（原发肿瘤中KRAS基因外显子2存在GGT->GTT突变，而肝转移灶为KRAS野生型），因此使用下一代测序技术并通过手工显微切割富集肿瘤细胞样本，对肝转移灶再次进行突变分析；确认与原发肿瘤为同一类型的突变（KRAS基因外显子2的GGT->GTT）。
准确的组织取样和足够灵敏的检测方法对于正确识别可接受抗EGFR单克隆抗体治疗的结直肠癌患者至关重要。
