High-grade neuroendocrine carcinomas of the lung express K homology domain containing protein overexpressed in cancer but carcinoid tumors do not
High-grade neuroendocrine carcinomas of the lung express K homology domain containing protein overexpressed in cancer but carcinoid tumors do not
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DOI：
10.1016/j.humpath.2006.11.011
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发表时间：
2007-04-01
期刊：
影响因子：
3.3
通讯作者：
Wang, Hanlin L.
中科院分区：
文献类型：
--
作者：
Xu, Haodong;Bourne, Patricia A.;Wang, Hanlin L.
K同源结构域蛋白是胰岛素样生长因子(IGF)信使RNA结合蛋白家族的一员，在胚胎发育和某些恶性肿瘤中均有表达。KOC被称为L523S和IGF信使RNA结合蛋白3，在我们用抗人KOC的单抗进行的免疫组织化学研究中发现，它在高级别肺神经内分泌癌中频繁表达。10例小细胞肺癌均呈胞浆强阳性，9例弥漫性阳性，1例局灶性阳性。14例大细胞神经内分泌癌(LCNECs)中，9例胞浆浓染弥漫性染色，5例局灶性胞浆内活动。而在21例典型和非典型类癌中，除1例非典型类癌嗜酸细胞胞浆染色较弱外，其余均未检测到KOC。尽管SCLCs的染色强度(90%)高于LCNECs(%)，但差异无统计学意义(P=.3408)。有趣的是，我们的免疫组织化学研究表明，IGF-11据报道受KOC调控，在小细胞肺癌、LCNEC以及典型和非典型类癌中表达相似，与肿瘤的KOC表达状态无关。这些结果支持KOC可能在高级别神经内分泌癌的生物学行为调节中发挥重要作用。此外，检测KOC表达可能有助于高级别神经内分泌癌与类癌的鉴别诊断。我们发现在KOC阳性的小细胞肺癌和LCNEC以及KOC阴性的类癌中，IGF-11的表达相同，这表明在这些肿瘤中IGF-11的表达调控机制不同。(C)2007 Elsevier Inc.保留所有权利。
K homology domain containing protein overexpressed in cancer (KOC) is a member of the insulin-like growth factor (IGF) messenger RNA-binding protein family and is expressed during embryogenesis and in certain malignancies. KOC, known as L523S and IGF messenger RNA-binding protein 3, was shown to be frequently expressed in high-grade neuroendocrine carcinomas of the lung in our immunohistochemical studies using a monoclonal antibody against human KOC. Specifically, all 10 small cell lung carcinomas (SCLCs) exhibited strong cytoplasmic staining, 9 with diffuse positivity and I with focal positivity. Among 14 large cell neuroendocrine carcinomas (LCNECs), 9 exhibited strong and diffuse cytoplasmic staining, and 5 cases showed focal inummoreactivity. In contrast, no KOC was detected in 21 typical and atypical carcinoids, except for one atypical carcinoid with oncocytic cells showing weak cytoplasmic staining. Although SCLCs exhibited a strong and diffuse staining pattern more frequently (90%) than LCNECs (64%), the difference did not reach statistical significance ( P=.3408). Interestingly, Our immunohistochemical studies demonstrated that IGF-11, reportedly regulated by KOC, was comparably expressed in SCLC, LCNEC, and typical and atypical carcinoids, irrespective of KOC expression status of the tumors. These results support the formulation that KOC may play an important role in the regulation of biologic behavior of high-grade neuroendocrine carcinomas. In addition, detection of KOC expression may be diagnostically useful in distinguishing high-grade neuroendocrine carcinomas from carcinoid tumors. Our findings of equivalent IGF-11 expression in KOC-positive SCLC and LCNEC and KOC-negative carcinoid tumors suggest different regulatory mechanisms involved in the control of IGF-11 expression in these tumors. (c) 2007 Elsevier Inc. All rights reserved.