First, thank you for the absolutely awesome site; I've been quietly following it ever since lung adenocarcinoma was recently found in a family member's unilateral pleural effusion.
Since she is almost 70, never smoker, East Asian, a cell block from a thoracentesis was tested for EGFR and ALK. It was found to be exon 19 deletion positive, L858R negative, ALK negative. However, it was only low level positive, with 4.5% mutant allele. The sensitivity of the test (RFLP) is 1-5%. There is a sentence that reads like a disclaimer: "Please note that the mutant allele is detected at a level of <10%".
I was wondering if this is just due to the nature of the sample (cytology report mentioned that there were few tumor cells, 30% of nucleated cells were tumor) or if it is a sign that most of the tumor is driven by something else?
Thanks!
Reply # - August 4, 2014, 10:58 AM
Reply To: Significance of mutant allele frequency on EGFR test
Hi snowyowl, I'm very sorry your family is going through this. I'll ask a doctor to reply.
From my understanding (which could be wrong) a test report is given only when there is enough tissue to give a complete picture.
All best,
Janine
Reply # - August 4, 2014, 11:42 AM
Reply To: Significance of mutant allele frequency on EGFR test
Hi snowyowl, welcome and thank you for posting. Cells in pleural effusions are often a mix of tumor cells along with inflammatory (immune) cells and reactive cells from the pleura called mesothelial cells, so the percentage of cells that are actually cancer may be relatively small. While EGFR tests have a limit to how SENSITIVE they are, i.e. they can miss a mutation if it is present at very low levels, they are quite SPECIFIC, i.e. you can believe a mutation is present if one is detected.
I think in this case the mutation is likely real, and just represents detection in a small number of cancer cells within a larger pool of normal cells. EGFR mutations are early events in cancer formation so I would not expect there to be multiple independent driver mutations in a single patient.