ABSTRACT
Merkel cell carcinoma (MCC) is a rare skin cancer with only limited therapeutic options for advanced disease. We previously showed that oncogene ALK is frequently expressed at the RNA level in MCC and further that ALK positivity by immunohistochemistry is frequent and correlates strongly with Merkel cell polyomavirus (MCPyV) positivity. In this study, we investigated whether ALK receptor is active in MCC tumor samples and MCC cell lines, and whether ALK would be a prospective treatment target in MCC. We utilized tissue microarrays constructed from 136 primary MCC tumor samples as well as nine previously established MCC cell lines to determine the presence of ALK and phosphorylated ALK (p-ALK) via immunohistochemistry. Almost half of the analyzed MCC tumors displayed ALK phosphorylation (47.8%). Analysis of MCC tumor samples revealed that the presence of p-ALK correlated to MCPyV positivity, younger age, nonexistence of metastases at diagnosis and ultimately to better MCC-specific survival. In contrast to MCC tumor samples only two out of nine MCC cell lines showed only low ALK phosphorylation by immunohistochemistry. Our study reveals clear disparity in ALK activity between patient derived tumors and cell line samples and therefore, more advanced disease models such as xenografts are necessary to resolve whether ALK is a useful treatment target in MCC.
Subject(s)
Anaplastic Lymphoma Kinase/metabolism , Carcinoma, Merkel Cell/metabolism , Carcinoma, Merkel Cell/mortality , Aged , Aged, 80 and over , Cell Line , Female , Humans , Male , PhosphorylationABSTRACT
The aim of this in vitro study was to explore light transmission through an individually formed fiber-reinforced composite (FRC) post compared with two prefabricated FRC posts. Three different glass FRC posts from different manufacturers were used: two groups included prefabricated glass FRC posts (RelyX and GC Fiber Posts) and one group consisted of individually formed E-glass FRC posts with semi-interpenetrating polymer network (semi-IPN) polymer matrix (everStick Post). Various lengths of posts and lightprotected cylinders were made. The specimens were light-polymerized on the test tray of a light radiance testing device (MARC Resin Calibrator). Light transmission in the direction of fibers was registered. Light transmission decreased with increasing post length (p≤0.001; ANOVA) up to 12 mm in all post groups. The individually formed FRC post showed highest light transmission in all cylinder lengths (p<0.001) compared to prefabricated FRC posts, which could benefit polymerization of post material and luting cement.