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Browsing by Author "Veija, Tuukka"

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  • ALK is frequently phosphorylated in Merkel cell carcinoma and associates with longer survival 
    Jaatinen, Jenni; Salmikangas, Marko; Böhling, Tom; Sihto, Harri; Koljonen, Virve; Veija, Tuukka (2021)
    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.
  • MicroRNA-34a underexpressed in Merkel cell polyomavirus –negative Merkel cell carcinoma tumors 
    Veija, Tuukka (2014)
    Introduction: Merkel cell carcinoma (MCC) is a rare neuroendocrine cancer of the skin that has a strong propensity to relapse and metastasize. Exposure to ultraviolet radiation and immunosuppression contribute to MCC. Merkel cell polyomavirus (MCV) is detected in 70% to 80% of MCC tumors, but the significance of MCV infection is not yet understood. MicroRNAs (miRNA) have been reported to associate with many types of cancer, and miRNA profiles of other cancers with a virus etiology have been defined. The aim of this study was to compare the expression of five miRNAs, miR-34a, miR-30a, miR-1539, miR-142-3p and miR-181d in formalin fixed paraffin embedded MCC tumor samples according to MCV status using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Materials and methods: Sufficient RNA was extracted from 26 tumor samples and from control skin sample using the miRNeasy FFPE Kit (QIAGEN, Valencia, CA, USA). Reverse transcription of the RNA was done using the miScript II RT Kit (50) (QIAGEN). QRT-PCR was executed with miScript SYBR Green PCR Kit (QIAGEN).and LightCycler 480 instrument (Roche Diagnostics GmbH, Mannheim, Germany). Student's t-test and Mann-Whitney U-test were used to evaluate differences in miRNA expression. Results: We found a statistically significant underexpression of mir-34a in MCV-negative tumors compared to MCV-positives. The other four miRNAs studied did not show significant expression differences according to MCV-status. There was no statistically significant difference in miRNA expression according to tumor location or metastasizing. Conclusion: The difference in miRNA expression according to MCV-status suggests distinct pathogenesis of the tumors. The role of underexpressed miR-34a in MCV-negative tumor pathogenesis remains unclear but it might be consequential in the tumorigenesis of MCV-negative tumors.

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