Colorectal poorly differentiated neuroendocrine carcinomas frequently exhibit BRAF mutations and are associated with poor overall survival

被引:49
作者
Olevian, Dane C. [1 ]
Nikiforova, Marina N. [1 ]
Chiosea, Simon [1 ]
Sun, Weijing [2 ]
Bahary, Nathan [2 ]
Kuan, Shih-Fan [1 ]
Pai, Reetesh K. [1 ]
机构
[1] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Med Ctr, Dept Internal Med, Div Med Oncol, Pittsburgh, PA 15213 USA
关键词
Colorectal; Neuroendocrine carcinoma; Mixed adenoneuroendocrine carcinoma; BRAF; KRAS; MSI; Overall survival; AGGRESSIVE ADENOCARCINOMA; CANCER; TUMORS; COLON; SUBTYPES; RAF;
D O I
10.1016/j.humpath.2015.11.004
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:124 / 134
页数:11
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