From: Hadi Yaziji <hadi@phenopath.com>
Date: Thu, 25 May 2000 19:17:54 -0700
To: <histonet@pathology.swmed.edu>
Subject: Re: Her-2/neu question

I am Dr. Gown's associate pathologist at PhenoPath Laboratories in 
Seattle.
I would like to share some facts that I think are important to know in 
order
to make an informed decision.

The antibody used in the Herceptest kit is the same good old polyclonal
antibody that Dako still sells as a separate antibody. The price 
difference,
as you know, was justified because of 'standardization' procedures that
include the use of cell pellets with known levels of protein expression. 
The
FDA approved 3 testing kits not for the exact same reasons:

Herceptest (Dako)           Suitability for Herceptin
PathVysion (Vysis)           Prognostic marker and predicting response to
standard chemo
Inform (Oncor/Ventana)  Prognostic marker

This is the reason Medicare in many states decided to reimburse Herceptin
treatment only if the detection was conducted using Herceptest. We 
published
a paper in the Journal of Clinical Oncology (August issue) showing the
significantly low level of specificity (high false-positive rate) of
Herceptest if the FDA-approved guidelines are used. It becomes specific 
only
when you 'normalize' the intensity of staining by considering the staining
intensity on benign epithelium as baseline negative (no matter how strong
the staining is). If there  is no SIGNIFICANT difference of staining, 
these
cases should be called negative, as we observed by FISH correlation 
studies.
I don't this is a problem that is restricted to Herceptest. Any
ultra-sensitive method will start picking up normal levels of HER-2/neu on
membranes of benign epithelium as well as tumors that are not
overexpressors.

Regarding Medicare patients, our approach is the following: Because 70-80%
of invasive tumors are negative, we cannot justify using Herceptest on 
every
Medicare patient. We run the same (lot cheaper) polyclonal antibody first.
If the results are negative, no further testing is needed. If they're
positive, we repeat them with Herceptest and we only charge for the 
latter.
We only do FISH in questionable cases. This will significantly cut down 
not
only the cost but also the tech time and the pathologist time.

If you need copies of our publications or if you want to discuss this
further, please don't hesitate to let me know.
I hope this helped.

Best regards, 
---------------------------------------------------
Hadi Yaziji, M.D.
PhenoPath Laboratories
3000 1st Avenue
Seattle, WA 98121
Phone: 206-374-9000
Fax:   206-374-9009
Web:   www.phenopath.com
     www.digitalclinic.com



I don't wish to distract from Jerry Santiago's question but the answer to
mine may impact what Jerry and others are doing.

Like Jerry (and others, I imagine), I am interested in exploring less
expensive options (than the Hercept kit from Dako) to provide Her2 neu
results. However, Dako is circulating a publication (Dako Hercept Test
Facts) that indicates that many states will not reimburse for HERCEPTIN
therapy (the treatment, not the test) unless the Hercept test is used to
determine patient eligibility. The states that seem to have such a policy
(according to Dako's publication) include:

Alabama, Arizona, Arkansas, Colorado, Connecticut, Florida (requires that
only FDA approved tests are used), Hawaii, Iowa, Louisiana, Nevada, New
Mexico, New York (similar requirement to Florida) North Dakota, Oklahoma,
Oregon, South Carolina,  South Dakota, Washington, Wyoming

This suggests to me that the use of less expensive antibodies to
determine a patient's Her2 neu status may not be possible if the
patient's treatment will not be covered.

I would appreciate a response from anyone who can shed further light on
this.

Vinnie




Vinnie Della Speranza
Manager for Anatomic Pathology Services
Medical University of South Carolina
165 Ashley Avenue
Suite 309
Charleston, SC  29425
ph:  (843) 792-6353
fax: (843) 792-8974
email: Dellav@musc.edu