FISH testing for HER2 2+ and 3+

I would like to talk about this, as time and again, I have been seeing people treated elsewhere, where they have received Herceptin for some time (where HER2 was 3+ on IHC), and then suddenly the FISH report comes negative.

For making it concise, I am not going to explain what is IHC and what is FISH and other details. You can google it up. I will stick to the point.

1. When is FISH done?

FISH is done for tumours which test '2+' on HER2 testing on IHC. HER2 has three possibilities o IHC:

1+ means negative

2+ means equivocal (could be negative or positive)

3+ means positive and will benefit from Herceptin.

So when on IHC, it is 2+, we are not very sure it is positive or negative and hence we do a confirmatory test - FISH

Remember, IHC is a pathologist dependent test. One pathologist may report it as 2+ and other pathologist may report it as 3+. A pathologist who is experienced in IHC and cancer reporting, is much less likely to make an error.

2. So when is Herceptin given?

Herceptin is given for those who are HER2 3+

3. Is IHC 3+ enough to give Herceptin? or is FISH mandatory for even IHC 3+ tumours?

According to worldwide guidelines, Herceptin can be given for IHC 3+ tumours, and FISH is not needed.

However, mark my words, the IHC has to be done by standardised labs and 'experienced' pathologists. This is where India faces a problem. If a substandard lab reports IHC as 3+ (which could be negative as well), we are risking a patient's life by giving Herceptin, as Herceptin, though beneficial from cancer point of view, can cause damage to heart.

It's extremely important here to stick to standard labs.

There are many so called 'standard' labs all over India, where only the name is standard, the pathologists keep on changing every few years. You see, its very very difficult to accept a IHC report from there. Even in a large city like Mumbai, there are barely 5 to 10 labs whom we can genuinely rely on IHC reports.

Hence, my team follows the following principle:

For IHC HER2 1+, no further testing.

FOR IHC HER2 2+, FISH is surely done.

FOR IHC HER2 3+, for most cases, we still do a FISH testing to confirm the positivity, unless the report is from Tata Memorial Centre or a few other places (Tata and some of these Hospitals have the best possible pathology reporting). The idea is, anyways, by giving Herceptin, the patient is going to spend more than 3 to 4 lakhs, apart from consequences of Herceptin on heart. FISH testing does not cost more than 15000 in standard places, and here, in some cases, we even get it free of charge. And the report does not take more than 7 days. So we wait, ensure that FISH is positive an only then give Herceptin.

And please note, this is the methodology of only my team. It is not a standard at all, and other oncologists may not agree to it, which is fairly fine enough.

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  • Brilliant post by Sumeet as always.....

    Explaining the Her2 testing and implication of its result.

    I completely agree that for IHC =0-1, FISH is not indicated and one would label them as Her2 negative.

    for IHC=2+ and 3+, many centres in UK did perform FISH routinely as a reflex action, despite the fact that IHC 3+ on its own was sufficient enough an indication to assume a patient to be Her 2 positive.

    In the Indian scenario, i perfectly understand and would personally follow this same mentioned algorithm of getting FISH for both Her 2 = 2+ as well as Her 2 = 3+, depending on the place where the report comes from.

    In the UK, i am aware of the strong Optimal internal (twice a year) & external (once a year) QA procedures along with the Optimal laboratory accreditation( every alternate year). The labs are suspended if there is any discordance or substandards detected.

    I am unsure of the Indian Regulations and its adherence here , and hence testing IHC 3+ patients with FISH test seems totally justified, when there is an element of uncertainty by an oncologist about the laboratory credentials.

  • Thanks Dr Sumeet and Dr Rohit for such valuable information. Personally, I'm very much interested in patient advocacy as well as in research legal and legislative. Thank u very much for this post.

  • Dear Doctor

    The above has been very informative. My wife was operated and initial investigation were done at Rajeev Gandhi Cancer Institute Delhi.

    the first chemotherapy and complete followon protocol was given by them ,ehich now is being followed for her.

    Quote stage pT2N3aM0

    ER 20% , PR -ve HER-2 neu-3+

    I donot know if any fish test was done but she has already undergone six chemotherapy and now every 21days cycle byceltis is being given which will befor ttal 17 cycles.

    I will like your opinion if this is ok.

    n Rajeev Gandhi Canmab was administered but now she is being given biceltis.

    She has taken the treatment witout any adverse effect.

    Will like your opinion on line of treament

    thanks

  • Hey psra. I too got my treatment at rgci. Lets share your no.

  • A very informative and logically clear post from Dr Sumeet. Thanks Dr. You have clearly delineated the ground position in our country, where everything is somewhat 'flexible' and people are 'accommodative'!

  • Dr. this is really good/detailed information...thanks dr..for your valuable time...

  • Doctors Sumeet & Rohit - Thanks for guidance & sparing your valuable time for us

  • icmr.nic.in/ijmr/2010/septe...

    The above link shows a research article by some doctors of Tata Memorial wherein on page 292 they mention that IHC score 3+ can be obtained, though rarely, even if there is no Her2 over expression due to polysomia of chromosome 17. Hence it would appear that FISH test is the gold standard. I would therefore believe it is best to insist on FISH test even if there is a score 3+ in IHC from an accredited lab even if our oncologist does not ask for it. After all it does not cost so much. I think Dr. Sumeet follows the safest procedure and he has given his reasons.

  • Thanks for that link above, greenbear. It's worthwhile reading that article.

  • Hi every one,

    For my mom HER2 is 3+ from pathology report.16 herceptin cycles are completed.we didnt do any FISH test.what happens if the HER2 is 2+ and given herceptin ?? whether she will get any side effects?

  • chandraa, do not worry, HER2 3+ is fine. It is only occasionally that we get problems.

    Don't let the above discussion bother you. Your mother has got the right treatment. Good that her treatment stands completed. Keep follow ups with your doc.

  • Ok we will do fallow up.Thanks doctor .

  • DR

    Thank u v much for the valuable information about HERpositive. I have the ihc

    report as HER2 neu 3+ How do we do FISH test? I s it done in the tumor removed which is stored in the lab? or is it done by any blood test?

    kindly let me know if i cantake this FISH test in Bangalore any authentic lab?

    kindly give your phone number Dr.if u dont object

  • Hi Tutu, FISH test is performed at pathology, they needs some tissue from your cancer. This can be from a biopsy or from when you had surgery to remove your cancer but i dont have any idea labs in banglore, hope some one else knows about it on the forum.

    Thanks

    Manish

  • Thank You Dr Sumeet Shah, it was a wonderful article , my friends sister from Yemen has

    HER2 NEU =+3 and our doctor insist for FISH test, unfortunately they are very poor people we cant manage the chemotherapy cost further than FISH test cost .

    you may know the situation in Yemen right now , is there is a chance to do this FISH test free in Mumbai , or what can you advise us

    Note : she has already take the first cycle (Docetaxel 140 mg + Biceltis 640)

  • Hi welcome to our forum

    If she is poor there is one scheme Rajiv Gandhi Jeevandayee Arogya Yojana (RGJAY) - where the treatment is free. See is she can avail the same

  • I appreciate your concern, abdullaomeer. The question is not about getting FISH free or not, question is affordability of Biceltis / Herceptin. SInce managing chemotherapy cost is presently an issue for your friend's sister, I believe, getting Herceptin will be much more of a problem, since it costs five to ten times the chemotehrapy cost. The total cost of Herceptin will go beyond 3 to 4 lakhs (minimum), whereas FISH costs some 10k to 15k. Medical Oncologists can have coupons to get the FISH for free, you can ask your Medical Oncologist. Also, there are times when company whose molecule you use (Biceltis or Herceptin or others), will do the FISH test for free for you. Again, the person to contact here is your medical oncologist. If he talks for you, your work can get done.

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