Wei Qing, Wang Xicheng, Gao Jing, Li Jian, Li Jie, Qi Changsong, Li Yanyan, Li Zhongwu, Shen Lin
Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
PLoS One. 2016 Jun 14;11(6):e0156659. doi: 10.1371/journal.pone.0156659. eCollection 2016.
We performed a retrospective study to assess the clinicopathological characters, molecular alterations and multigene mutation profiles in colorectal cancer patients with signet-ring cell component.
Between November 2008 and January 2015, 61 consecutive primary colorectal carcinomas with signet-ring cell component were available for pathological confirmation. RAS/BRAF status was performed by direct sequencing. 14 genes associated with hereditary cancer syndromes were analyzed by targeted gene sequencing.
A slight male predominance was detected in these patients (59.0%). Colorectal carcinomas with signet-ring cell component were well distributed along the large intestine. A frequently higher TNM stage at the time of diagnosis was observed, compared with the conventional adenocarcinoma. Family history of malignant tumor was remarkable with 49.2% in 61 cases. The median OS time of stage IV patients in our study was 14 months. RAS mutations were detected in 22.2% (12/54) cases with KRAS mutations in 16.7% (9/54) cases and Nras mutations in 5.4%(3/54) cases. BRAF V600E mutation was detected in 3.7% (2/54) cases. As an exploration, we analyzed 14 genes by targeted gene sequencing. These genes were selected based on their biological role in association with hereditary cancer syndromes. 79.6% cases carried at least one pathogenic mutation. Finally, the patients were classified by the percentage of signet-ring cell. 39 (63.9%) cases were composed of ≥50% signet-ring cells; 22 (36.1%) cases were composed of <50% signet-ring cells. We compared clinical parameters, molecular and genetic alterations between the two groups and found no significant differences.
Colorectal adenocarcinoma with signet-ring cell component is characterized by advanced stage at diagnosis with remarkable family history of malignant tumor. It is likely a negative prognostic factor and tends to affect male patients with low rates of RAS /BRAF mutation. Colorectal patients with any component of signet-ring cells, regardless of the extent, shared similar clinicopathological characteristics, molecular alterations and genetic profiles.
我们进行了一项回顾性研究，以评估伴有印戒细胞成分的结直肠癌患者的临床病理特征、分子改变和多基因突变谱。
2008年11月至2015年1月期间，61例连续的伴有印戒细胞成分的原发性结直肠癌患者可供病理确诊。通过直接测序检测RAS/BRAF状态。通过靶向基因测序分析与遗传性癌症综合征相关的14个基因。
这些患者中男性略占优势（59.0%）。伴有印戒细胞成分的结直肠癌在大肠中分布良好。与传统腺癌相比，诊断时观察到TNM分期通常更高。61例中有49.2%的患者有显著的恶性肿瘤家族史。我们研究中IV期患者的中位总生存时间为14个月。在22.2%（12/54）的病例中检测到RAS突变，其中KRAS突变占16.7%（9/54），NRAS突变占5.4%（3/54）。在3.7%（2/54）的病例中检测到BRAF V600E突变。作为一项探索，我们通过靶向基因测序分析了14个基因。这些基因是根据它们与遗传性癌症综合征相关的生物学作用选择的。79.6%的病例至少携带一种致病突变。最后，根据印戒细胞的百分比对患者进行分类。39例（63.9%）由≥50%的印戒细胞组成；22例（36.1%）由<50%的印戒细胞组成。我们比较了两组之间的临床参数、分子和基因改变，未发现显著差异。
伴有印戒细胞成分的结直肠腺癌的特征是诊断时分期较晚，有显著的恶性肿瘤家族史。它可能是一个负面预后因素，倾向于影响RAS/BRAF突变率较低的男性患者。无论印戒细胞成分的范围如何，任何含有印戒细胞成分的结直肠癌患者都具有相似的临床病理特征、分子改变和基因谱。
