The diagnostic and biological implications of laminin expression in serous tubal intraepithelial carcinoma.
The diagnostic and biological implications of laminin expression in serous tubal intraepithelial carcinoma.
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DOI：
10.1097/pas.0b013e31825ec07a
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发表时间：
2012-12
期刊：
影响因子：
--
通讯作者：
Shih IeM
中科院分区：
文献类型：
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作者：
Kuhn E;Kurman RJ;Soslow RA;Han G;Sehdev AS;Morin PJ;Wang TL;Shih IeM
有令人信服的证据表明，浆液性输卵管上皮内癌（STIC）可能是盆腔高级别浆液性癌（HGSC）发展的主要部位。鉴定在STIC中上调的分子不仅对于提供生物标志物以帮助诊断STIC而且对于阐明我们对HGSC的发病机制的理解是重要的。在本研究中，我们通过RNA测序比较HGSC和正常输卵管上皮（FTE）的转录组，并确定LAMC 1编码层粘连蛋白γ1是HGSC相关的优先上调基因之一。RT-PCR进一步验证了与正常FTE相比，HGSC中的LAMC 1上调。对32例HGSC与STIC同时存在的病例进行免疫组化染色。后者根据形态学、TP 53突变、p53和Ki-67免疫组化模式进行诊断。在所有病例中，与邻近的FTE相比，发现STIC和HGSC中的层粘连蛋白γ1免疫染色强度显著更高（p< 0.001）。在正常FTE中，层粘连蛋白γ1免疫反应性主要位于纤毛细胞的基底膜或顶面，而在STIC和HGSC细胞中，层粘连蛋白γ1染色在整个细胞质中弥漫且强烈。更重要的是，在所有13个由于无效突变而缺乏p53免疫反应性的STIC中检测到强烈的层粘连蛋白γ1染色。这些结果表明，层粘连蛋白γ1免疫反应性的过度表达及其染色模式的改变可以作为一个有用的组织生物标志物，特别是对于那些p53阴性和Ki-67标记指数低的STIC。
There is compelling evidence to suggest that serous tubal intraepithelial carcinoma (STIC) is the likely primary site for the development of pelvic high-grade serous carcinomas (HGSCs). Identifying molecules that are upregulated in STIC is important not only to provide biomarkers to assist in the diagnosis of STIC but also to elucidate our understanding of the pathogenesis of HGSC. In this study, we performed RNA sequencing to compare transcriptomes between HGSC and normal fallopian tube epithelium (FTE), and identified LAMC1 encoding laminin γ1 as one of the preferentially upregulated gene associated with HGSC. RT-PCR further validated LAMC1 upregulation in HGSC as compared to normal FTE. Immunohistochemistry was performed on 32 cases of concurrent HGSC and STIC. The latter was diagnosed based on morphology, TP53 mutations, p53 and Ki-67 immunohistochemical pattern. Laminin γ1 immunostaining intensity was found to be significantly higher in STIC and HGSC compared to adjacent FTE in all cases (p< 0.001). In normal FTE, laminin γ1 immunoreactivity was predominantly localized in the basement membrane or on the apical surface of ciliated cells whereas in STIC and HGSC cells, laminin γ1 staining was diffuse and intense throughout the cytoplasm. More importantly, strong laminin γ1 staining was detected in all 13 STICs which lacked p53 immunoreactivity due to null mutations. These findings suggest that the overexpression of laminin γ1 immunoreactivity and alteration of its staining pattern in STICs can serve as a useful tissue biomarker, especially for those STICs that are negative for p53 and have a low Ki-67 labeling index.