The Molecular Microscope (MMDX R ) interpretation of thoracic and abdominal allograft biopsies: Putting things in perspective for the clinician

The Molecular Microscope System (MMDXR ) has significant potential to enhance biopsy interpretation. However, discussions of MMDx do not acknowledge the basic accuracy of histology readings, and the ability of pathology as a stand-alone tool to guide patient management. MMDx overstates its ability to automatically correct for problems in biopsy readings. Assertions of accuracy approaching 99% are not supported by "real world" data. The high rate of discrepancies between MMDx® and standard biopsy readings can be attributed to the summation of many factors other than histology interpretation, including molecular noise, assay thresholding, limited sensitivity of microarray technology for low expression genes, errors in classifier development, narrow data interpretation, and lack of spatial context. It is not widely recognized that molecular signatures are not disease-specific and are affected by the stage of disease as well as the extent of tissue injury. The effect of sampling error on MMDx performance is significantly under-estimated, particularly in heart and lung biopsies. Therefore, MMDx reports should always be interpreted in the context of conventional biopsy readings. The clinical picture and conventional biopsy reading should be allowed to over-ride the molecular interpretation when there is concern that confounding factors are at play.