[EXTERNAL] [IMPROVEDX] genotypes/phenotype

Peggy Zuckerman peggyzuckerman at GMAIL.COM
Fri Apr 6 23:24:27 UTC 2018


I also appreciate this important discussion, as I am a Renal Cancer patient
advocate, and see the tremendous variation in the information as to the
basic pathology reports provided to patients.  When that pathology is not
described as clear cell, with no other features,  one might assume that the
pathology is correct.  However, when those reports mention any other of the
known subtypes, rare subtypes, and/or unusual features or characteristics,
I recommend that the patient request a second opinion from a larger
academic center.  It is stunning to see how many changes there can be in
those initial reports, once reviewed.

When there were no options but high dose interleukin following surgery, it
may not have mattered too much what the pathology was, as there was too
little too offer the patient to  delve into the pathology, it would seem.
However, that situation still continues, with patients' varying subtypes
not be described, and therefore, not using that information to choose
treatments. And with the obvious lack of appropriate care.

Certainly, there are patients who reach out to clinical trials when they
seek more experienced care.  Using the erroneous or inadequte path report
can prevent a patient from entering a trial, perhaps turned away due to
that error.  Other trial teams may be willing to review the slides and
refine the pathology report, especially when they are seeking those with
the rarer subtypes. It would be instructive to know what percentage of path
reports are considered to be in error at trial sites.

It is bad enough to have a generally rare  cancer, as most of the renal
cell carcinomas are, but especially disheartening when the patient is NOT
diagnosed properly.  The issue raised by Dr. Samuel as to the genetic and
genomic testing will further challenge the urologists, pathologist and
oncologists who lack RCC experience.

The issues I raise with RCC have their parallels with many other cancers.
This has to be addressed very urgently, as without a precise diagnosis,
there is no precision medicine.

Sincerely,
Peggy Zuckerman

Peggy Zuckerman
www.peggyRCC.com

On Fri, Apr 6, 2018 at 2:26 PM, Samuel, Rana <Rana.Samuel at va.gov> wrote:

> There is another source of variance that needs to be considered first: If
> you send the same sample (split) to different labs - one lab's may report
> that a mutation is present while the other lab may report that there is no
> mutation, or that a different mutation is present. So one reason for the
> differing phenotype may be that the genotype is incorrect!
>
> We have a LONG way to go before we get to standardization and
> reproducibility of genetic test results between differing analytic
> platforms. Even among pathologists (the supposed-to-be experts on lab
> tests) there is very slow dissemination and even slower uptake, of the
> limits of analytic and clinical validity of these tests. At this time, the
> cottage industry of homegrown tests being marketed under the umbrella of
> 'precision medicine' is exploding, and unfortunately, the designated
> gatekeeper (the FDA) does not have the resources or the mandate to ensure
> rigorous proof of analytic and clinical validity, especially between
> competing systems/platforms ostensibly looking for the same genes.
>
> See references attached above, especially the highlighted paragraph from
> the "Quality Assurance in Genetic testing" section on page 5 of the 2015
> ASCO statement published in the JCO.
>
> Great forum. The multidisciplinary input, especially from patient
> advocates, is exemplary.
>
> Rana Samuel, MD, FCAP
> Chief, Pathology and Laboratory Medicine Service (PALMS, 113)
> Lead pathologist - VISN 2
> VA western New York Healthcare System (VAWNYHS)
> 3495 Bailey Avenue, Buffalo, NY 14215
> Ph:    716-862-8701
> Fax:  716-862-7824
> Rana.samuel at va.gov
>
>
>
> -----Original Message-----
> From: Robert Bell [mailto:0000000296e45ec4-dmarc-request at LIST.
> IMPROVEDIAGNOSIS.ORG]
> Sent: Friday, April 06, 2018 1:22 PM
> To: IMPROVEDX at LIST.IMPROVEDIAGNOSIS.ORG
> Subject: [EXTERNAL] [IMPROVEDX] genotypes/phenotype
>
> Dear all,
>
> Following up on the genetic aspects of diagnosis with mutations, I am told
> that with the same mutation/genotype the phenotype can sometimes differ. I
> would welcome confirmation of this.
>
> How do dIagnostic skills handle differing phenotypes with the same
> genotype? What contribution to error does that produce?
>
> Rob Bell M.D.
>
> Sent from my iPad
>
>
>
>
>
> Moderator: David Meyers, Board Member, Society to Improve Diagnosis in
> Medicine
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