[Histonet] Re: HER-2

[Mark Tarango]

HER2 FISH really is considered the best method.  It's the only method that
has actually been tied directly to patient outcome.  The other methods are
expert consensus based.  That being said, there are some cases that are
equivocal by FISH.

Sometimes we have to ignore the CEP-17 (green) signals and report the HER2
status based only the HER2 copy number.  If the HER2/CEP17 ratio is
equivocal but the average HER2 count is over 6, we add a comment explaining
that it can be considered positive.  If it's between 4-6, we say
it's equivocal and usually suggest repeating on the excision.  If it's
under 4, we say that it can be considered to be negative.  We can resolve
most cases this way.  In rare instances we have sent out to another lab to
perform alternative FISH probes to enumerate for chromosome 17 (probes
SMS/RARA to Phenopath).  We have not found this to be especially useful.

If a case is 3+ by IHC but for some reason the oncologist wants FISH to
confirm, the patient will not be treated if FISH is negative.  There could
be other reasons besides gene amplification for accumulation or expression
of the HER2 protein.  The drug is only proven to work when the gene is
amplified and you test that by FISH.

PCR has it's own problems too.  The biggest thing, I think, is that you
dilute your HER2 score by including normal tissue during macro or
micro-dissection.  This does not work well for small foci of tumor.  Many
stomach and esophagus biopsies contain only small amounts of tumor.

Mark

On Wed, Feb 6, 2013 at 7:03 AM, Bob Richmond <rsrichmond <@t> gmail.com> wrote:

> Mark Tarango notes:
>
> >>Many pathologists, if they have any doubt about the score will just say
> that it is 2+ so that its gets HER2 by FISH which is considered the best
> method for determining HER2 status.<<
>
> On one busy pathology service I worked in 2004-2006 we were quite
> explicit about overcalling HER-2 by IHC 2+. If we had any doubts at
> all, we sent out the FISH. The cost is trivial compared to the cost of
> treating a woman with trastuzumab (Herceptin).
>
> It's important to understand that IHC and FISH do not measure the same
> thing - IHC is looking at the excessive amount of the gene product,
> while FISH is looking at amplification of the gene itself. Neither is
> necessarily the "best method". Some oncologists want both methods done
> on all cases.
>
> PCR further complicates the situation. I think some reference labs now
> consider this the preferred HER-2 method for adenocarcinomas of the
> stomach and esophagus.
>
> Bob Richmond
> Samurai Pathologist
> Maryville TN
>
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