Non‐Coding RNAs in Diagnostic Pathology of High Grade Central Osteosarcoma

The histological evaluation remains the cornerstone of diagnosing highly malignant osteosarcoma, having demonstrated its efficacy and reliability over several decades. However, even in recent times misdiagnoses with severe consequences, including inadequate surgical procedures, have persisted. Consequently, there is a considerable need to enhance diagnostic security further. Adjunct immunohistochemical approaches have proven highly effective in cancer diagnostics generally but have been limited in their utility for differentiating highly malignant osteosarcoma. Molecular genetic findings have significantly improved the diagnosis of Ewing’s sarcoma by identifying specific translocations and chondrosarcoma by detecting specific IDH-gene mutations. However, molecular genetic alterations in highly malignant osteosarcoma exhibit a very high degree of complexity, limiting their diagnostic utility. Given that only 1-2% of the human genome consists of protein-coding sequences, the increasing number of non-coding regulatory RNAs, which are increasingly being described, has garnered significant attention in the field of clinical cancer diagnostics. Over the past several years, patterns of altered non-coding RNA expression have been identified that facilitate the distinction between benign and malignant tumors in various organs. In the field of bone tumors, the experience with this approach has been limited so far. Divergent expression of microRNAs has demonstrated utility for differentiating osteosarcoma from osteoblastoma and discriminating osteosarcoma from giant cell tumor of bone and fibrous dysplasia. However, the application of non-coding(nc)RNA expression patterns for the differential diagnosis of osteosarcoma is still in its nascent stages. This review provides an overview of the current status of ncRNAs in osteosarcoma diagnostics, in conjunction with histological evaluation. The potential of this approach is discussed in detail.