Olevian Dane C, Nikiforova Marina N, Chiosea Simon, Sun Weijing, Bahary Nathan, Kuan Shih-Fan, Pai Reetesh K
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213.
Department of Internal Medicine, Division of Medical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213.
Hum Pathol. 2016 Mar;49:124-34. doi: 10.1016/j.humpath.2015.11.004. Epub 2015 Nov 17.
The molecular alterations in colorectal poorly differentiated neuroendocrine carcinoma remain incompletely characterized, particularly with respect to mutations in BRAF and KRAS. We analyzed 32 colorectal poorly differentiated neuroendocrine carcinomas and 40 colorectal poorly differentiated conventional adenocarcinomas for mutations in KRAS and BRAF and for DNA mismatch repair protein abnormalities to correlate histopathology with molecular alterations and survival. Compared with poorly differentiated conventional adenocarcinoma, poorly differentiated neuroendocrine carcinoma frequently harbored BRAF mutations (59% versus 5%; P < .001) and less frequently demonstrated KRAS codon 12 or 13 mutations (17% versus 43%; P = .03). BRAF mutations were identified in both pure poorly differentiated neuroendocrine carcinoma (60%) and poorly differentiated neuroendocrine carcinoma associated with a signet ring cell adenocarcinoma component (82%). Most (93%) poorly differentiated neuroendocrine carcinomas demonstrated proficient DNA mismatch repair by either microsatellite instability polymerase chain reaction or DNA mismatch repair immunohistochemistry. Patients with poorly differentiated neuroendocrine carcinoma had a significantly worse overall survival compared with patients with poorly differentiated conventional adenocarcinoma (P < .001). There was no significant difference in overall survival between patients with pure poorly differentiated neuroendocrine carcinoma and patients with both poorly differentiated neuroendocrine carcinoma and adenocarcinoma components (P = .5). In conclusion, colorectal poorly differentiated neuroendocrine carcinomas frequently harbor BRAF mutations and are associated with poor overall survival.
结直肠低分化神经内分泌癌的分子改变仍未完全明确，尤其是在BRAF和KRAS突变方面。我们分析了32例结直肠低分化神经内分泌癌和40例结直肠低分化传统腺癌的KRAS和BRAF突变以及DNA错配修复蛋白异常情况，以将组织病理学与分子改变及生存情况相关联。与低分化传统腺癌相比，低分化神经内分泌癌常伴有BRAF突变（59%对5%；P <.001），而KRAS密码子12或13突变的发生率较低（17%对43%；P =.03）。BRAF突变在单纯低分化神经内分泌癌（60%）和伴有印戒细胞腺癌成分的低分化神经内分泌癌（82%）中均有发现。大多数（93%）低分化神经内分泌癌通过微卫星不稳定性聚合酶链反应或DNA错配修复免疫组化显示DNA错配修复功能正常。与低分化传统腺癌患者相比，低分化神经内分泌癌患者的总生存期明显更差（P <.001）。单纯低分化神经内分泌癌患者与同时患有低分化神经内分泌癌和腺癌成分的患者的总生存期无显著差异（P =.5）。总之，结直肠低分化神经内分泌癌常伴有BRAF突变，且与较差的总生存期相关。
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