| Autor: |
Jun, Sun-Young, Kim, Misung, Jin Gu, Mi, Kyung Bae, Young, Chang, Hee-Kyung, Sun Jung, Eun, Jang, Kee-Taek, Kim, Jihun, Yu, Eunsil, Woon Eom, Dae, Hong, Seung-Mo |
| Zdroj: |
Modern Pathology; April 2016, Vol. 29 Issue: 4 p402-415, 14p |
| Abstrakt: |
Activating KRASand/or BRAFmutations have been identified as predictors of resistance to anti-epidermal growth factor receptor (EGFR) chemotherapy in colorectal cancer. But the status of KRASand BRAFmutations and their clinicopathologic and prognostic significance has not been extensively evaluated in small intestinal adenocarcinomas. In this work, the KRASand BRAFgenes in 190 surgically resected small intestinal adenocarcinoma cases were sequenced and their association with various clinicopathologic variables, including survival of the patients, was analyzed. KRASor BRAFmutations were observed in 63 (33%) cases. Sixty-one cases had KRASmutations and 2 had BRAFmutations and the two types of mutation were mutually exclusive. The majority of KRASmutations were G>A transition (43/61 cases, 71%) or p.G12D (31/61 cases, 51%). The patients with mutant KRAStended to have higher pT classifications (P=0.034) and more frequent pancreatic invasion (P=0.020) than those with wild-type KRAS. Multivariate logistic regression analysis showed that certain mutated KRASsubtypes (G>A transitions and G12D mutations) were significantly correlated with higher pT classification (P=0.015 and 0.004, respectively) than wild-type KRASand other KRASmutations. The patients with KRASor BRAFmutation had a tendency to shorter overall survival than those with wild-type KRASand BRAF(P=0.148), but subgroup analysis demonstrated the patients with KRASmutations showed worse survival (median, 46.0 months; P=0.046) than those with wild-type KRAS(85.4 months) in lower pT classification (pT1–pT3) group. In summary, KRASand, infrequently, BRAFmutations are observed in a subset of small intestinal adenocarcinomas, and are associated with higher pT classification and more frequent pancreatic invasion. KRASmutation is a poor prognostic predictor in patients with lower pT classification tumors. Anti-EGFR targeted therapy could be applied to about two-thirds of small intestinal adenocarcinoma patients, namely those with wild-type KRASand BRAFif they have metastatic disease, similar to colorectal cancer patients. |
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