Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis
Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis
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DOI：
10.1038/modpathol.3800659
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发表时间：
2006-10-01
期刊：
影响因子：
7.5
通讯作者：
Nakatani, Yukio
中科院分区：
文献类型：
--
作者：
Hiroshima, Kenzo;Iyoda, Akira;Nakatani, Yukio
肺大细胞神经内分泌癌和小细胞癌的区别在某些情况下是困难的。有些人认为这些癌应归类为一种高级别神经内分泌癌。我们研究了小细胞癌（n=23），大细胞神经内分泌癌（n=17）和经典大细胞癌（n=12）的生物学特征。小细胞癌肿瘤细胞核直径与淋巴细胞核直径的平均比值小于大细胞神经内分泌癌（P < 0.0001）。CD 56、mASH 1、TTF-1和p16在小细胞癌中的表达频率高于大细胞神经内分泌癌，而NeuroD的表达频率低于大细胞神经内分泌癌。高级别神经内分泌癌的3 p杂合性缺失频率高于经典大细胞癌（P=0.0002）。D5 S422（5 q33）等位基因丢失在小细胞癌中比在大细胞神经内分泌癌中更常见（P=0.0091）。典型大细胞癌、大细胞神经内分泌癌和小细胞癌患者的肿瘤平均分数区域丢失指数分别为0.38、0.65和0.72（P=0.0003）。经典型大细胞癌、大细胞神经内分泌癌和小细胞癌I期患者的5年总生存率分别为67%、73%和60%。在大细胞神经内分泌癌中，NeuroD表达的患者生存率较高，而p63表达的患者生存率较低。TTF-1表达的患者在小细胞癌中的生存率较差。我们的数据表明，大细胞神经内分泌癌和小细胞癌是不同的形态，表型和遗传，虽然有一些重叠的功能。虽然需要进一步的研究来分析高级别神经内分泌癌的生物学行为，包括对化疗的敏感性，但大细胞神经内分泌癌与小细胞癌的病理学区别可能是治疗神经内分泌肿瘤患者所必需的。
The distinction between pulmonary large cell neuroendocrine carcinoma and small cell carcinoma is difficult in some cases. Some propose that these carcinomas should be classified as one high-grade neuroendocrine carcinoma. We examined biological features of small cell carcinoma (n=23), large cell neuroendocrine carcinoma (n=17), and classic large cell carcinoma (n=12). The average ratio of nuclear diameter of the tumor cells to that of lymphocytes for small cell carcinoma was smaller than that for large cell neuroendocrine carcinoma (P < 0.0001). The frequencies of the expressions of CD56, mASH1, TTF-1, and p16 were higher and that of NeuroD was lower in small cell carcinoma than in large cell neuroendocrine carcinoma. The frequency of loss of heterozygosity at 3p was higher in high-grade neuroendocrine carcinomas than in classic large cell carcinoma (P=0.0002). Allelic losses at D5S422 (5q33) were more frequent in small cell carcinoma than in large cell neuroendocrine carcinoma (P=0.0091). Mean fractional regional loss indices of the tumors were 0.38, 0.65, and 0.72 for patients with classic large cell carcinoma, large cell neuroendocrine carcinoma, and small cell carcinoma, respectively (P=0.0003). Five-year overall survivals of patients with classic large cell carcinoma, large cell neuroendocrine carcinoma and small cell carcinoma in stage I were 67, 73, 60%, respectively. Patients with NeuroD expression had better survivals, and those with p63 expression had poorer survivals in large cell neuroendocrine carcinoma. Patients with TTF-1 expression had poorer survivals in small cell carcinoma. Our data suggest that large cell neuroendocrine carcinoma and small cell carcinoma are different morphologically, phenotypically, and genetically, although there are some overlapping features. Although further studies are needed to analyze the biological behavior of high-grade neuroendocrine carcinomas including sensitivity to chemotherapy, the pathological distinction of large cell neuroendocrine carcinoma from small cell carcinoma may be necessary to treat the patients with neuroendocrine tumors.