Significance of the ALK Marker in non-smoker lung cancer patients

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Published: 11 Mar 2011
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Prof Ping Yang - Mayo Clinic, Rochester, USA
Non-smoker lung cancer sufferers who test positive for the ALK (anaplastic lymphoma kinase) marker have a more aggressive form of cancer that is considerably more likely to progress and recur. Prof Ping Yang discusses the IHC and FISH techniques that are used to detect the ALK marker and explains when clinicians can use IHC and when it is necessary to use FISH. Prof Yang outlines the prevalence of the ALK marker within non-smoker lung cancer patients and talks about the potential for targeted therapies to treat this patient population.

European Multidisciplinary Conference in Thoracic Oncology (EMCTO 2011) 24—26th February 2011, Lugano

Significance of the ALK Marker in non-smoker lung cancer patients

Professor Ping Yang – Mayo Clinic, Rochester, USA


Professor Ping Yang, you’re from the Mayo Clinic, we’re lucky to have you here in Europe at the Lugano meeting. You’ve been discussing here anaplastic lymphoma kinase status, now that’s a marker and it’s to do with patients who are never smokers who get lung cancer. Could you explain what this is all about?

This is a study trying to examine how frequent this particular marker presented in a subgroup of lung cancer patients. It has been previously reported to be more prevalent in never smokers and in adenocarcinoma, that’s the study we tried to really accurately estimate what’s going on in the subgroup.

And if you’re a never smoker and you get lung cancer and you have the ALK positive marker, what have you discovered that this implies?

We found that this marker, representing a subgroup of tumour, is more aggressive in nature, for example, higher disease stage and poor differentiation.

And how big a difference does the marker make?

This marker is really showing this group of patients would have a doubled risk for having disease progression and recurrence.

So that’s a very powerful indicator of the outlook for that patient. Now interestingly you’ve been looking at assessing ALK status, either by immunohistochemistry or by FISH, fluorescence in situ hybridization. What are the differences between those two techniques and what does all of this mean for the clinician?

Right now the gold standard is by FISH but IHC is a more accessible test for clinicians. So the first round, we think, in our study is using IHC and then for some ambiguous categories by IHC, that means one positivity and two positivity by scoring, should go on for FISH for confirmation.

And have you found that there is concordance between these two techniques?

Yes, we’ve found 100% concordance, one IHC is as three positivity and FISH positive. Or IHC scored zero and then FISH scored negative, those are being in 100% concordance. So that explains about three-quarters of the patients already, so only a quarter of the patients who are in-between IHC zero and IHC three should go on for FISH confirmation.

So you could use the IHC initially and then go on to FISH if you need to. This gives you, if it’s positive, a doubling of the risk for progression. What would that imply clinically for your patient?

Right now we do not have a concrete answer to that yet, but we are just thinking that these patients should be more aggressively treated.

Among non-smokers, it’s a difficult question, but the prevalence of this ALK positivity in the population, will that indicate anything also?

Do you mean in the patient population?

In the patient population and in the general population.

In the general population we do not have any data because this is a marker for the lung tumour. So for the lung cancer patients where we can get the tumour, we know it’s more prevalent in the never smoker population and our estimates are really pointing to around 10%.

So what do you think busy cancer doctors should be doing about this finding of yours about ALK positivity being a negative indicator?

I’m thinking that if there is a targeted drug developed, this could be a candidate for a potentially effective drug towards this marker but right now we have no treatment indication yet.

So it’s a prognostic at the moment but until an agent has been developed, a directed agent, you can’t necessarily take full advantage of that?

That’s right, yes. Not mature yet for any action.

So what do you think doctors should take home from your presentation here?

Just to stay tuned to see if any effective targeted drug could be on the market soon.

Well Professor Yang, thank you very much for joining us on

It’s a pleasure to be here.