Combined large cell neuroendocrine carcinoma and endometrioid carcinoma of the endometrium: a shared gene mutation signature between the two histological components
Combined large cell neuroendocrine carcinoma and endometrioid carcinoma of the endometrium: a shared gene mutation signature between the two histological components
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DOI：
10.1007/s13691-016-0263-9
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发表时间：
2017-01-01
影响因子：
0.7
通讯作者：
Miyagi, Etsuko
中科院分区：
文献类型：
--
作者：
Ariura, Masayo;Kasajima, Rika;Miyagi, Etsuko
一名61岁的日本女性被诊断为FIGO IB期子宫内膜样癌（EC）合并大细胞神经内分泌癌（LCNEC）。右支气管肺区、纵隔和脑的淋巴结转移也被发现。患者最终发展为胸膜炎和癌性心包炎，并在手术后51个月死于癌症。由于子宫神经内分泌癌的基因畸变仍不清楚，我们研究了50个选定的癌症相关基因的突变热点的改变。EC和LCNEC成分在PTEN、PIK3CA和FGFR3中具有相同的改变。EC和LCNEC成分均在CTNNB1上存在杂合SBSs，但密码子不同（EC为G34R， LCNEC为T41A）。改变的基因特征提出了EC和LCNEC成分来自共同前体病变的可能性。LCNEC独立获得了显著的CTNNB1突变，淋巴结转移起源于该成分。由于LCNEC成分似乎带来了疾病的侵袭性过程并定义了患者的预后，因此需要进一步的研究来阐明NE癌在子宫内膜内发展的机制。
A 61-year-old Japanese woman was diagnosed with FIGO Stage IB endometrioid cancer (EC) combined with large cell neuroendocrine carcinoma (LCNEC). Metastasis to the lymph nodes in the right bronchopulmonary area, mediastinum and brain were also identified. The patient eventually developed pleuritis and pericarditis carcinomatosa, and died of cancer at 51 months after surgery. Because gene aberrations in uterine neuroendocrine carcinoma are still not well understood, we examined alterations in the mutational hotspots of 50 selected cancerassociated genes. The EC and LCNEC components shared identical alterations in PTEN, PIK3CA and FGFR3. Both the EC and LCNEC components had heterozygous SBSs on CTNNB1 but at different codons (G34R in EC, and T41A in LCNEC). The altered gene signature raised a possibility that the EC and LCNEC components were derived from a common precursor lesion. The LCNEC independently obtained a significant CTNNB1 mutation and the lymph node metastasis originated from this component. Because the LCNEC component seemed to bring about the aggressive course of the disease and defined the patient outcome, further investigations are needed to elucidate the mechanism of NE carcinoma development in the endometrium.