Previous studies indicated that this 15-percent point fell in a clear gap between tumors that were obviously ALK-positive and tumors that were obviously ALK-negative, making it an attractive threshold.
"But what this study shows is that when you look not at tens, but hundreds of cases, tumors clearly exist that come right up to the 15-percent cutoff point," Camidge says.
Another possible gray area is when a gene rearrangement occurs but is very complex – like shuffling cards rather than just cutting the deck. In this situation the typical separated dot pattern indicative of ALK rearrangement may not be present, but instead doublets or triplets of single or un-separated dots may exist. This atypical cellular footprint can tell an expert that, while officially ALK-negative, the cancer has made some changes in the region of the ALK gene that could still make the cancer sensitive to ALK-inhibitor drugs.
“We believe these data suggest that such borderline and atypical negative cases deserve a closer look, perhaps with new kinds of diagnostic tests," says Camidge.
The current study tested 1426 samples of non-small cell lung cancer, which included 174 officially positive for an ALK rearrangement and 1252 that were officially negative. Of the ALK-negative tumors, 121 had greater than 10 percent ALK-positivity, but were still below the 15 percent needed to classify the overall tumor as ALK-positive. This means that 8.5 percent of non-small cell lung cancers were "borderline" negative. In the study, 1-2 percent also showed atypical-negative patterns, a group that may also benefit from a closer re-evaluation of their ALK status.
Early in 2013, serendipity provided a chance to test whether at least one of the Colorado team’s hypotheses were correct. In a case described in an upcoming article in the Journal of Thoracic Oncology, Dr. Shengxiang Ren from the Shanghai
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