Frequent and Specific Involvement of Changes of the p16-RB Pathway in Esophageal Neuroendocrine Carcinoma

Frequent and Specific Involvement of Changes of the p16-RB Pathway in Esophageal Neuroendocrine Carcinoma
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DOI:
10.21873/anticanres.13302
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发表时间:
2019-04-01
影响因子:
2
通讯作者:
Takimoto, Masafumi
Takimoto, Masafumi
中科院分区:
医学4区
文献类型:
--
作者:
Fujimasa, Koichiro;Ohike, Nobuyuki;Takimoto, Masafumi

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目的:本研究调查了视网膜母细胞瘤(RB)蛋白和p16蛋白的免疫组织化学表达在10个神经内分泌癌(NEC),比较两个混合型NEC,28鳞状细胞癌(SCC),和12例食管癌患者的癌细胞瘤(CS)。材料与方法:免疫组织化学染色采用抗生物素蛋白-生物素复合物检测法。染色被评价为弥漫阳性、异质性(5-95%的肿瘤细胞)或弥漫阴性。结果如下:RB的弥漫性丢失和p16的弥漫性过表达的组合在所有NEC中被发现(10/10),这在高度侵袭性的恶性肿瘤中被发现,并被认为令人信服地表明p16-RB通路的变化。相比之下,没有混合型NEC,一个SCC和一个CS显示了这一发现。在7例NEC中检测到共存的上皮内癌,只有1例病变显示弥漫性RB丢失和p16过表达。结论:这些数据表明,p16-RB通路的变化是普遍和特异性参与食管NEC的发展和侵袭,它可能是一个有用的诊断标志物和潜在的治疗靶点。
Aim: This study investigated the immuno histochemical expression of retinoblastoma (RB) protein and p16 protein in 10 neuroendocrine carcinomas (NECs), in comparison to two mixed-type NECs; 28 squamous cell carcinomas (SCCs), and 12 carcinosarcomas (CSs) from patients with esophageal cancer. Materials and Methods: Immunohistochemical staining was performed using the avidin-biotin complex detection method. The staining was evaluated as diffusely positive, heterogeneous (in 5-95% of tumor cells), or diffusely negative. Results: The combination of a diffuse loss of RB and the diffuse overexpression of p16, which is found in highly aggressive malignant tumors and is considered to convincingly suggest changes in the p16-RB pathway, was found in all NECs (10/10). In contrast no mixed-type NECs, one SCC and one CS showed this finding. Coexisting intraepithelial carcinoma was detected in seven NECs and only one lesion showed the combination of diffuse RB loss and p16 overexpression. Conclusion: These data suggest that changes in the p16-RB pathway were universally and specifically involved in the development and invasion of esophageal NECs and that it may be a useful diagnostic marker and a potential therapeutic target.