Abstract
Purpose
Melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) can be used as a unique model to identify molecular mechanisms to distinguish rarely metastatic (BCC), often metastatic (SCC) and most metastatic (melanoma) cancer. It is known that epithelial–mesenchymal transition and stemness transcription factors (TWIST1, SNAI2/SLUG, and BMI1) play an important role in metastasis and their dysregulation has been demonstrated in metastatic cancers. We hypothesized that this spectrum of cutaneous cancers (BCC, SCC, and melanoma) would be a unique cancer model system to elucidate steps toward cancer invasion and metastasis.
Methods
We evaluated the mRNA expression level of BMI1, TWIST1, and SNAI2/SLUG and studied clinicopathological features in 170 skin cancers along with normal tissue samples.
Results
We demonstrate downregulation of BMI1 mRNA expression in BCC samples compared with controls (p = 0.0001), SCC (p = 0.001), and melanoma (p = 0.0001) samples. Downregulation of TWIST1 mRNA expression is seen in only BCC samples compared with controls (p = 0.031). High SNAI2 mRNA expression is represented in melanoma samples compared with controls (p = 0.022) and SCC samples (p = 0.031). High mRNA expression of TWIST1 is seen in patients with positive history of cancers. Extremely low mRNA expression of BMI1 is detected in patients with positive history of cancers other than skin cancer.
Conclusions
These findings provide support for the hypothesis that the spectrum of cutaneous cancers could be better understood as a series of gene dosage-dependent entities with distinct molecular events. Oncogene-induced senescence, mechanism of which is still unclear, could be one explanation for these results.
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Acknowledgments
We thank staff of Tumor Clinic, Pathology Department and the Department of Plastic and Reconstructive Surgery, Razi Dermatology Hospital for their help in sample and clinical information collection.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Vand-Rajabpour, F., Sadeghipour, N., Saee-Rad, S. et al. Differential BMI1, TWIST1, SNAI2 mRNA expression pattern correlation with malignancy type in a spectrum of common cutaneous malignancies: basal cell carcinoma, squamous cell carcinoma, and melanoma. Clin Transl Oncol 19, 489–497 (2017). https://doi.org/10.1007/s12094-016-1555-4
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DOI: https://doi.org/10.1007/s12094-016-1555-4