MicroRNAs may revolutionize NSCLC classification

February 3, 2010 – 11:54 am by Colette Pilkus

Routine histophathology is the gold standard method of non-small cell lung cancer classification, but this method is considered unreliable, with poor reproducibility and low observer correlation. Studies show that when given the same sample, pathologists will disagree on the diagnosis in 30% to 40% of cases in classifying non-small cell lung squamous samples. Studies have also shown the limitations of gold standard histopathology methods as well as with immunohistochemical staining methods for classifying NSCLC.

The reason for this is that a lot of pathologists are looking through the microscope and deciding based on what they see about the suplification of non-cell lung cancer, according to Ronen Tamir, chief commercialization officer for Rosetta Genomics.

“This is completely subjective and is completely open to interpretation,� Mr. Tamir says. “Studies even show that when you show the same pathologist slides at different times of the day and on different days they will not always give you the same answer. The reason is that it’s a subjective view of the architecture of the tumor, in the way the cell looks, the way it’s arranged, and the way the nucleus looks when its arranged versus a molecular test, where they look at the contents of the cell. The subjectivity plays a big role in the way that diagnostics is played today.�

MicroRNAs are coming to light as playing a major role in gene expression. Rosetta Genomics is using its miReview technology platform to harness the power of microRNA’s that may revolutionize the standard of medical care. miRview squamous, which is offered in the United States by Prometheus Laboratories under the brand name ProOnc squamous, is a microRNA-based molecular assay that classifies NSCLC into squamous or non-squamous carcinomas using the expression level of a single microRNA biomarker. The company’s miRview test correctly classified 95% of fine-needle aspirate specimens originally diagnosed as poorly differentiated NSCLC into squamous or non-squamous.

MicroRNAs’ unique advantage as biomarkers lies in their high tissue specificity and their exceptional stability in the most routine preservation methods for biopsies, including formalin-fixed paraffin embedded (FFPE) block. The small size of microRNAs enables them to remain intact in FFPE blocks, as opposed to messenger RNA, which tends to degrade rapidly in samples preserved by this method. In addition, early preclinical data has shown that by controlling the levels of specific microRNAs, cancer cell growth may be reduced.

In the miRview study, 102 resected NSCLC samples were classified at Johns Hopkins University School of Medicine using gold standard methods (H&E staining) and a panel of immunohistochemical stains, and later classified in a blinded fashion using Rosetta’s miRview squamous test. The samples were classified as either squamous or non-squamous cell carcinoma. Results showed 100% concordance between the diagnoses established by methods exceeding the gold standard methods and miRview squamous for the resected NSCLC samples.

Mr. Tamir believes that the results show not only the potential of miRview, but also the potential of micorRNA’s in molecular diagnostics and the potential of Rosetta Genomics to harvest this data and to develop the data into clinical assays.

“What we’ve seen at Rosetta is an increase in the sensitivity as well as in the depth of the search for drug companies looking for the right biomarkers and the right assay to help them with patient certification,� Mr. Tamir tells R&D Directions. “The environment is really supportive of that, and we’ve seen in the last 12 months an increase of that activity.�

Tags: microRNAs, miRview, NSCLC, Rosetta Genomics