I've been reading the postings on HER2-related issues. Allow me to
address the fixation-related issues.
1. Overfixation: 48 versus 72 hours of fixation has no difference on
the impact of protein or gene signal. The CAP guidelines will most
likely be revised to increase the upper limit of cutoff to 72 hours.
That said, overfixation seems to have some impact on hormone
receptors, and given that every invasive breast cancer should be
tested for both HER2 and hormone receptor, then people will need to
address the upper limit of fixation time.
2. Undrefixation: This what really has had devastating effects on the
quality of HER2 testing by IHC. The literature is there, but it's the
usual, good-old literature published by Fox and others in the 80s and
90s. Everyone knows that formaldehyde penetrates the tissue at a very
rapid rate of 1 mm/hour (more or less depending on fat content and
other factors). But infiltration is NOT equal to fixation. The 6-hour
minimum fixation requirement should be strictly adhered to. There is
currently a loop hole in the minimum requirements for fixing core
biopsies versus excision specimens. Cores are required to be fixed
for a minimum of 1 hour. That will change to. The revised guidelines
will most likely increase that to 6 hours. This is a very realistic
and scientifically sound requirement.
We wrote a document to help colleagues address various issues related
to the impact on the guidelines on their lab. It can be found on our
Hadi Yaziji, M.D., Medical Director
Vitro Molecular Laboratories
7000 62nd Avenue, PH-C
Miami, FL 33143
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