Three-dimensional visualization of perlecan-rich neoplastic stroma induced concurrently with the invasion of oral squamous cell carcinoma
Three-dimensional visualization of perlecan-rich neoplastic stroma induced concurrently with the invasion of oral squamous cell carcinoma
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DOI：
10.1111/jop.12184
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发表时间：
2014-09-01
影响因子：
3.3
通讯作者：
Saku, Takashi
中科院分区：
文献类型：
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作者：
Maruyama, Satoshi;Shimazu, Yoshihito;Saku, Takashi
背景：我们已经证明了在口腔鳞状细胞癌（SCC）开始侵袭时和侵袭后诱导富perlecan间质。然而，目前尚不清楚这种肿瘤间质是如何在肿瘤组织中排列的。方法：为此，利用数字图像和图像分析软件对组织微阵列样本进行三维分析，其中角蛋白和perlecan通过免疫组织化学对比标记，以证明SCC灶与perlecan阳性间质间隙之间的关系或原位癌（CIS）与浸润性SCC灶之间的关系。结果：三维重建显示癌细胞病灶内(I)区和外(O)区有三种模式：模式1、模式1(+)/模式O-；模式2,1 (+)/O+；模式3为1(-)/O+。CIS和SCC表面肿块均可见模式1。模式2可见于小的SCC病灶，在二维切片上似乎是孤立的，但在三维重建中大多与肿瘤肿块连续。模式3仅限于小的鳞状细胞癌灶，这是真正从肿瘤肿块中分离出来的。结论：二维SCC病灶分离不能视为侵袭性，而被perlecan阳性基质（模式2和模式3）包围的SCC病灶可视为更客观的SCC侵袭性指标。这是第一个由口腔SCC侵袭引起的肿瘤间质空间的3D组织水平演示，我们已经根据之前的2D和组织培养证据预测了其存在。
BACKGROUND: We have demonstrated the induction of perlecan-rich stroma of oral squamous cell carcinoma (SCC) on and after its start of invasion. However, it remains unknown how such a neoplastic stroma is actually arranged in tumor tissues.METHODS: To this end, tissue microarray samples, in which keratin and perlecan were contrastively labeled by immunohistochemistry, were three-dimensionally analyzed using digital images and image analysis software to demonstrate the relationship between SCC foci and the perlecan-positive stromal space or that between carcinoma in situ (CIS) and invasive SCC foci.RESULTS: The three-dimensional (3D) reconstruction demonstrated three kinds of perlecan profiles for inside (I) and outside (O) areas of the carcinoma cell focus: mode 1, 1(+)/O-; mode 2, 1(+)/O+; and mode 3, 1(-)/O+. Mode 1 was seen in CIS as well as SCC tumor massifs in the surface part. Mode 2 was seen in small SCC foci, which seemed isolated in 2D sections but were mostly continuous with the tumor massif in 3D reconstructions. Mode 3 was limited to small SCC foci, which were truly segregated from the tumor massif.CONCLUSIONS: The results indicated that the 2D SCC focus isolation could not be regarded as invasion but that the SCC foci surrounded by perlecan-positive stroma (modes 2 and 3) could be regarded as a more objective measure for invasion of SCC. This is the first 3D tissue-level demonstration of the neoplastic stroma space induced with oral SCC invasion, the presence of which we have predicted based on our previous 2D and tissue culture evidence.