Re: Interpretation of HER-2 FISH Results

From:Richard Cartun

Dear Bob:

Actually, the case was sent to us for consultation; I am not sure if we
qualify as "Big League", but I think we can certainly "play ball".  The
patient has an invasive tubular carcinoma, nuclear grade I, histologic
grade I (ER+/PR+) along with the extensive DCIS that showed 3+ HER-2/neu
protein overexpression.

R. Cartun


>>>  05/02/02 03:01PM >>>
Richard Cartun notes:

>>The topic of "who should interpret HER-2 FISH results" has recently
been 
discussed on Histonet. - I just finished looking at a case of breast CA
where 
the invasive mammary duct CA was negative for HER-2/neu protein 
overexpression, but the ductal carcinoma in-situ (DCIS) was 3+
positive. It 
was a very impressive specimen; the HER-2 positive DCIS surrounded the
small 
focus of HER-2 negative invasive tumor. As you may already know, 
determination of ER/PR/HER-2 status should be performed on invasive
tumor; 
not carcinoma in-situ. I don't have a problem with non-MD's doing the 
interpretation of the FISH results (keep in mind that I am a Ph.D.),
but 
whoever does the interpretation must know which cells to
evaluate. By all means, if there are questions regarding the
interpretation 
of the FISH slides, go to the pathologist who signed-out the case and
ask 
them to identify the tumor for evaluation. I requested FISH on this
specimen 
for HER-2/neu gene amplification for academic purposes. Let's see if
the 
correct tumor cells are evaluated!<<

This result doesn't surprise me, since other adverse prognostic
criteria 
(starting with nuclear morphology) are often more striking in DCIS than
in 
invasive cancer. I'm not surprised that HER-2 FISH follows this path
also. 
I'm more concerned about >>the small focus of HER-2 negative invasive 
tumor<<. The big league breast pathologists - particularly David L.
Page at 
Vanderbilt - are getting more and more reluctant to call such small
foci near 
high-grade DCIS invasive cancer, and this case may need to be sent out
for 
consultation.

I'm not surprised to see FISH results interpreted by non-pathologists,
since 
in general new technology in pathology isn't done by pathologists. The

question the next generation will have to deal with is whether the
whole 
procedure should be done by non-pathologists. Fortunately, I shall have
been 
gathered to my grandfathers by then.

Bob Richmond
Samurai Pathologist
Knoxville TN





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