Maruyama Satoshi, Shimazu Yoshihito, Kudo Tomoo, Sato Kaori, Yamazaki Manabu, Abé Tatsuya, Babkair Hamzah, Cheng Jun, Aoba Takaaki, Saku Takashi
Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital, Niigata, Japan.
J Oral Pathol Med. 2014 Sep;43(8):627-36. doi: 10.1111/jop.12184. Epub 2014 Apr 4.
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.
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.
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, I(+)/O(-) ; mode 2, I(+)/O(+) ; and mode 3, I(-)/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.
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.
我们已经证明，口腔鳞状细胞癌（SCC）在开始侵袭时及之后会诱导富含基底膜聚糖的基质形成。然而，这种肿瘤基质在肿瘤组织中实际是如何排列的仍不清楚。
为此，通过免疫组织化学对比标记角蛋白和基底膜聚糖的组织微阵列样本，使用数字图像和图像分析软件进行三维分析，以展示SCC病灶与基底膜聚糖阳性基质空间之间的关系，或原位癌（CIS）与侵袭性SCC病灶之间的关系。
三维（3D）重建显示了癌细胞灶内部（I）和外部（O）区域的三种基底膜聚糖分布模式：模式1，I（+）/O（-）；模式2，I（+）/O（+）；模式3，I（-）/O（+）。模式1见于CIS以及表面部分的SCC肿瘤块。模式2见于小的SCC病灶，这些病灶在二维切片中看似孤立，但在三维重建中大多与肿瘤块连续。模式3仅限于真正与肿瘤块分离的小SCC病灶。
结果表明，二维SCC病灶分离不能被视为侵袭，而被基底膜聚糖阳性基质包围的SCC病灶（模式2和3）可被视为SCC侵袭的更客观指标。这是首次在组织水平上对口腔SCC侵袭诱导的肿瘤基质空间进行三维展示，我们此前基于二维和组织培养证据预测了其存在。
