Recently, NCI announced the launch of a clinical trial known as MARVEL (Marker Validation of Erlotinib in Lung Cancer) that hopes to find the biomarkers that may identify patient candidates for the class of EGFR tyrosine kinase small molecule inhibitors. EGFR FISH and KRAS mutations are among the biomarkers that will be evaluated in this trial. This study also hopes to provide guidance on how different EGFR biomarkers correlate to each other and their associations with clinical outcomes.
At TMD, we offer both the EGFR FISH and KRAS mutation assessment in a GLP and GCP laboratory. Recently, TMD completed the EGFR FISH assessment of a 480 patient Phase III lung cancer trial. We were able to complete the trial in a 30 day period (we think it’s a great turnarond time) and collected the data in the fashion prescribed by Dr. Fred Hirsch (University of Colorado Health Science Center). Specifically, EGFR positive specimens are defined as:
• EGFR gene to CEP 7 ratio ≥ 2
• Small gene cluster (4-10 copies) or innumerable tight gene cluster in > 10% of the tumor cells independent of the EGFR to CEP 7 ratio
• Larger and brighter EGFR signals than CEP 7 signals in >10% of the tumor cells while EGFR signals are smaller than the CEP 7 signals in the adjacent stromal and reactive cells independent of the EGFR to CEP 7 ratio
• > 15 copies of the EGFR signals in > 10% of the tumor cells independent of the EGFR to CEP 7 ratio
• Specimens with ≥ 40% of cells displaying ≥ 4 copies of the EGFR signal
We have found that the quality of tissue plays a critical role in the success of the EGFR FISH assay. Please contact us if you have an interest in the EGFR FISH testing on colon or other solid tumors.
The TMD website offers abundant information for KRAS testing. While the KRAS mutation story emerged out of colon cancer, the interest in lung cancers is rapidly growing. There are some significant differences. Colon biopsies tend to be easily available. Lung tumor material is much more challenging to obtain. Thus, the upfront assessment of the sufficiency of tumor for a KRAS mutation assay is very important. The DxS assay (CE-approved in Europe) detects 7 mutations that cover approximately 97% of the oncogenic KRAS mutations reported in colon cancer. This may not be the case with lung cancer where preliminary publications indicate these 7 mutations cover approximately 92% of the reported oncogenic mutations.
Stay tuned to our website and blogs for additional information on EGFR FISH and KRAS testing. We have several KRAS mutation trials kicking off at the end of the year and we look forward to solving further questions in this exciting arena with you.