Rich,
Thank you for your insight on EGFR.  Indeed it will be interesting to see
how this all comes out in a year or so.  I hope that we all continue to
share our experiences so that we can do the best we can for the patients
involved.  I am so pleased that the DAKO kit does not require HIER and uses
enzyme digestion instead.  HIER for her2 has been a night mare for those of
us at altitude.
Best regards,
Patsy

-----Original Message-----
From: histonet-bounces@lists.utsouthwestern.edu
[mailto:histonet-bounces@lists.utsouthwestern.edu]On Behalf Of Richard
Cartun
Sent: Sunday, March 14, 2004 10:57 AM
To: histonet@lists.utsouthwestern.edu
Subject: [Histonet] EGFR - My thoughts


Approximately two years ago, I said to my colleagues that EGFr testing
would make HER-2/neu testing look like "a walk in the park" (i.e, very
simple).  We tested DAKO's EGFR kit back then and compared it to the
monoclonal that we were using at the time (clone 31G7 from Zymed).
Although the results were similar (but not identical), the mAb from
Zymed consistently produced stronger immunoreactivity which was easier
to evaluate.

Like you, we have received many requests during the past 3 weeks from
our clinical colleagues to test their patients' colorectal tumors for
EGFR so that they can be considered eligible for treatment with
"Erbitux" (the anti-EGFR mAb drug).  Although I started with the Zymed
mAb, I am now convinced that this testing must be performed with
DakoCytomation's "EGFR pharmDx" kit (primarily for reimbursement
issues).  Although the kit works well, I find the resulting
immunoreactivity very difficult to score (this is true with the Zymed
mAb as well).  Most tumors have shown what I call "wishy-washing"
staining that, if it were HER-2, I would call it negative.  However, we
are instructed to score it 1+ "Positive".  I find it difficult to
believe that "Erbitux" will help a patient whose tumor shows rare to
focal immunoreactivity and often less intense than normal cells present
in the same  tissue section; however, I am not familiar with the
clinical trials and patient outcomes.  I have also noticed EGFR
variability from block to block in the same patient when we have tested
multiple tissue blocks.  In addition, in my experience, it is very
unusual to find a tumor that shows the classic "3+" staining pattern
that we see with c-erbB-2 (HER-2/neu protein) in breast CA's with
obvious gene amplification.

It will be interesting to see where we are 6 months to a year from now
with EGFR testing.

Richard Cartun
Director, Immunopathology
Hartford Hospital
Hartford, CT

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