Does anyone read IHC for MSI?

[green mantis]

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I was wondering if anyone here read IHC for the 4 MSI markers. I just got a request to do one on a biopsy, which I don't think is ideal. The oncologist wanted to know prior to treatment because the status of the markers may change. I know that I'm supposed to check for presence or absence in the tumor & compare it to the surrounding tissue (which would be better left for the resection).

I'd like to get your thoughts. I could probably send it out, but that opens up another bag of worms.


----- Antony

 

[moodydoc]

You would need to look at MLH1, PMS2, MSH2, and MSH6. The stains themselves can be a little problematic to set up. We do need to look at the tumor as well as the surrounding tissue. Similar to ER and PR in breast cancer, we cannot say there is loss of express without an internal tissue control. It is our policy to perform these stains on all new colon cancer (generally I mean the excision unless they are going to receive neo-adj. in which we will perform the stains on the biopsy). Also we batch our MSI stains and perform them once a week. There can be changes in the MSI protein expression, especially MSH6 after therapy.

 

[2121115]

You would need to look at MLH1, PMS2, MSH2, and MSH6. The stains themselves can be a little problematic to set up. We do need to look at the tumor as well as the surrounding tissue. Similar to ER and PR in breast cancer, we cannot say there is loss of express without an internal tissue control. It is our policy to perform these stains on all new colon cancer (generally I mean the excision unless they are going to receive neo-adj. in which we will perform the stains on the biopsy). Also we batch our MSI stains and perform them once a week. There can be changes in the MSI protein expression, especially MSH6 after therapy.

We do the stains on all new colon carcinomas; however, we perform them on the colectomy specimen and I have never been asked to do one on a biopsy.

 

[Enkidu]

What is the importance of these markers? Also, why are some markers done automatically and incorporated into the pathology report and other markers are done on the request of the oncologist? Are the ones done on request not supported enough to incorporate into normal procedure?

Edit: Ah, I see MSI = microsattelite instability. Why can't the molecular genetic test be done from the biopsy?

 

[sirenomelia]

You would need to look at MLH1, PMS2, MSH2, and MSH6. The stains themselves can be a little problematic to set up. We do need to look at the tumor as well as the surrounding tissue. Similar to ER and PR in breast cancer, we cannot say there is loss of express without an internal tissue control. It is our policy to perform these stains on all new colon cancer (generally I mean the excision unless they are going to receive neo-adj. in which we will perform the stains on the biopsy). Also we batch our MSI stains and perform them once a week. There can be changes in the MSI protein expression, especially MSH6 after therapy.

Is there a reason to do this on a sigmoid cancer in a 75 year-old that is obviously not a familial associated neoplasm?

 

[pathstudent]

Is there a reason to do this on a sigmoid cancer in a 75 year-old that is obviously not a familial associated neoplasm?

Yes. It is called 88342X4 AKA bilking the system. I hope Medicare and private insurance and self-pays have the sense to not pay your bull **** charge on the majority of those cases. It is this type of behavior that wastes taxpayer money and jacks up insurance premiums. MMR screening only is only indicated if patient is under 50 or perhaps up to 60 but doing it on every single case is offensive and abusive.

 

[path19]

Yes. It is called 88342X4 AKA bilking the system. I hope Medicare and private insurance and self-pays have the sense to not pay your bull **** charge on the majority of those cases. It is this type of behavior that wastes taxpayer money and jacks up insurance premiums. MMR screening only is only indicated if patient is under 50 or perhaps up to 60 but doing it on every single case is offensive and abusive.

Offensive and abusive...unless you care about picking up the 15% of sporadic colon cancers that result from defective mismatch repair proteins and will therefore have a better prognosis and likely won't respond as well to certain chemotherapeutic agents. Our oncologists do care about picking up this population, and I've heard they do at many other institutions as well.

 

[pathstudent]

Offensive and abusive...unless you care about picking up the 15% of sporadic colon cancers that result from defective mismatch repair proteins and will therefore have a better prognosis and likely won't respond as well to certain chemotherapeutic agents. Our oncologists do care about picking up this population, and I've heard they do at many other institutions as well.

Really? so a typical mod diff colon pt1 cancer in an 80 year old warrants testing. Your oncologists sound like a bunch of *****s.

Since when did oncologists know anything about the appropriate ordering of pathology tests anyway.

Can you please support your practice by a recommendation by an authoritative source such as cap or asco that says every single colon cancer should be tested for mmr by Ihc.

 

[path19]

Really? so a typical mod diff colon pt1 cancer in an 80 year old warrants testing. Your oncologists sound like a bunch of *****s.

Since when did oncologists know anything about the appropriate ordering of pathology tests anyway.

Can you please support your practice by a recommendation by an authoritative source such as cap or asco that says every single colon cancer should be tested for mmr by Ihc.

Caveat: I don't have a complete understanding of the literature on this subject, but the following is what I've learned from doing a quick search tonight, and I think it corroborates what I've heard discussed at various tumor boards

First regarding Lynch, check out this seminal paper from NEJM.
N Engl J Med 2005;352;1851
Using a cutoff of 50 years would have missed almost half of the Lynch patients (10/23), and a cutoff of 60 years would have missed 5/23. Admittedly, an n of 23 isn't overwhelming but I was surprised at how old some of those patients were (There was an 87 year old!)

Next, regarding the predictive/prognostic aspect of MSI testing:
J Natl Compr Canc Netw 2011;9:13-25 sums things up pretty well.
It's a pretty settled issue that MSI status provides prognostic information. It's debatable as to whether the value this provides to patients is worth the cost of 4 stains. I guess our oncologists have decided that it is.
What is also debatable is its ability to predict response to chemotherapy, although it seems like the data is sufficient enough for NCCN to recommend testing, at least for stage II disease.

And lastly, here is a CAP publication on the issue
http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2FcontentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}=committees%2Ftechnology%2Fmicrosatellite_testing.html&_state=maximized&_pageLabel=cntvwr

 

[2121115]

Offensive and abusive...unless you care about picking up the 15% of sporadic colon cancers that result from defective mismatch repair proteins and will therefore have a better prognosis and likely won't respond as well to certain chemotherapeutic agents. Our oncologists do care about picking up this population, and I've heard they do at many other institutions as well.

Agree. Oncologists care. And so do the many academic centers that also have this policy.

 

[moodydoc]

Yes. It is called 88342X4 AKA bilking the system. I hope Medicare and private insurance and self-pays have the sense to not pay your bull **** charge on the majority of those cases. It is this type of behavior that wastes taxpayer money and jacks up insurance premiums. MMR screening only is only indicated if patient is under 50 or perhaps up to 60 but doing it on every single case is offensive and abusive.

wow... angry little man...

This was a protocol that we suggested to the oncologists, whom agree. The information not only provides risk factors for family members but also provides prognostic and treatment information. We have recently had a 76 year old with loss of MMR proteins.

Also on my academic high horse (or my ivory tower view) it should be the pathologist who is proactive about bringing up test, recommending reflex testing, and yes denying tests. In general we need to play a more active role in such cases as this.

Another challenge with MMR testing is ensuring appropriate follow-up and possible genetic counseling. We have an information sheet that is give to each patient that undergoes excision that discusses what the results mean, as well as a number for the genetic counselors. If the patient is positive then the patient receives a referral to the genetic counseling team.

If we wanted to "bilk" the system we would have all prostate biopsies submitted separately and do PIN4 stains on all of them - a practice I have seen at larger commercial labs as well as a few smaller private practice places.

 

[2121115]

If we wanted to "bilk" the system we would have all prostate biopsies submitted separately and do PIN4 stains on all of them - a practice I have seen at larger commercial labs as well as a few smaller private practice places.

Academics always think that PP's are "bilking" the system, when in reality they are just underpaid for their services and then they try to find a reason to justify it.

 

[sbp]

several academic and non-academic places in the tri-state area do the stains... my institution is currently setting them up... I agree that some of the stains are a little difficult to run we are having that problem now with setting them up...

the idea is to do it on all stage 2 or more... (pt2 n+, or pt3 and up) .. like previous posts said it matters for treatment.... and as a side point for family screening as well....

just to point something out it is cheaper to do the msi immuno for screening that the PCR

 

[Alteran]

Yes. It is called 88342X4 AKA bilking the system. I hope Medicare and private insurance and self-pays have the sense to not pay your bull **** charge on the majority of those cases. It is this type of behavior that wastes taxpayer money and jacks up insurance premiums. MMR screening only is only indicated if patient is under 50 or perhaps up to 60 but doing it on every single case is offensive and abusive.

I so rarely jump into the fray, but I'm going to echo what's already been said. The sum total of the professional component for 4 88342s is roughly $200 assuming its Medicare. That is an insignificant drop in the bucket compared to the cost of treatment and eventual complications and hospitalizations. These tests are performed to hopefully avert some of these complications and save the patient the complications of wrong treatment (and god forbid some money on futile treatment). And for someone who apparently knows something about pathology, you seem to believe that all diseases "read the book". If this is the rigid thinking you've adopted, I truly feel sorry for the patients you'll be diagnosing.

 

[Adrian Cocot]

Just an FYI. You don't need to do all 4 IHCs. PMS2 and MSH6 will suffice.

 

[Euchromatin]

Offensive and abusive...unless you care about picking up the 15% of sporadic colon cancers that result from defective mismatch repair proteins and will therefore have a better prognosis and likely won't respond as well to certain chemotherapeutic agents. Our oncologists do care about picking up this population, and I've heard they do at many other institutions as well.

Our institution will shortly begin doing IHC for the four MMR proteins on all new resection cases as well. My understanding is that this 15% or so of sporadic (non-Lynch syndrome) cases with methylation causing decreased expression of MMR genes can easily be missed otherwise and they, overall, have a better prognosis that other sporadic colon cancers and don't respond as well to 5-FU therapy.

 

[sbp]

doing only 2 immunos will not suffice there will be missed cases...

 

[Adrian Cocot]

doing only 2 immunos will not suffice there will be missed cases...

http://www.ncbi.nlm.nih.gov/pubmed/21499234

 

[deleted314957]

I was wondering if anyone here read IHC for the 4 MSI markers. I just got a request to do one on a biopsy, which I don't think is ideal. The oncologist wanted to know prior to treatment because the status of the markers may change. I know that I'm supposed to check for presence or absence in the tumor & compare it to the surrounding tissue (which would be better left for the resection).

I'd like to get your thoughts. I could probably send it out, but that opens up another bag of worms.


----- Antony

we do and people have been successfully sued for NOT doing it when indicated and NOT suggesting genetic consultation when appropriate.

 

[KCShaw]

And people wonder why physicians shotgun order everything that ever comes to mind.

Not saying it necessarily applies with this -- I don't keep up with this specifically, and certainly sometimes some tests can save against unnecessary treatment -- but I still get the sense that one questioning phone call from a lawyer can lead entire systems to spend substantially more than would necessarily be indicated for standard of care. Not least because 'standard of care' can be subjective and fluid, and at times driven by academics looking for individual zebras or holier-than-thouness rather than those trying to run an efficient system for the masses.

 

[gbwillner]

Our institution will shortly begin doing IHC for the four MMR proteins on all new resection cases as well. My understanding is that this 15% or so of sporadic (non-Lynch syndrome) cases with methylation causing decreased expression of MMR genes can easily be missed otherwise and they, overall, have a better prognosis that other sporadic colon cancers and don't respond as well to 5-FU therapy.

Do you have a reference for that (that non-Lynch MMR+ cancers have a better prognosis)? If so, I guess there would be value in this blanket test.

The downside I see when NOT indicated (i.e., no suspicion of Lynch syndrome based on Amsterdam II criteria or other hunch) is unnecessary work-ups for those 15% of patients. Since 95% of Lynch syndrome is caused by mutations in MHL1 or MSH2, you are going to have to start sequencing these genes to r/o Lynch syndrome. Plus, there are the rare cases when there are other mutations.... all for some sporadic mutation that may be meaningless.