What are tissue microarrays?
Tissue microarrays are produced by a method of re-locating tissue from
conventional histologic paraffin blocks such that tissue
from multiple patients or blocks can be seen on the same
slide. This is done by using a needle to biopsy a standard
histologic sections and placing the core into an array
on a recipient paraffin block. This technique, originally
described by in 1987 by Wan, Fortuna and Furmanski in Journal
of Immunological Methods. They published a modification
of Battifora's "sausage" block technique whereby tissue
cores were placed in specific spatially fixed positions
in a block. The technique was popularized by Kononen and
colleagues in the laboratory of Ollie Kallioneimi after
a publication in Nature Medicine in 1998. This technology
should not be confused with DNA microarrays where each
tiny spot represents a unique cloned cDNA or oligonucleotide.
In tissue microarrays, the spots are larger and contain
small histologic sections from unique tissues or tumors.
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Figure 1 shows an example of a tissue microarray and its
construction. The arrays are assembled by taking core needle “biopsies” from
specific locations in pre-existing paraffin-embedded tissue
blocks and re-embedding them in an arrayed “master” block,
using techniques and an apparatus developed by Konenen et
al. In this way, tissue from 600 specimens can be represented
in a single paraffin block.
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Figure 2 shows an overview of a completed colon cancer
array and higher magnification views of spots from this array
and a melanoma array. Stains shown in these examples include
hematoxylin and eosin and DAB based-immunoperoxidase. The
current Beecher Instruments arraying device is designed to
produce sample circular spots that are 0.6mm in diameter
at a spacing of 0.7-0.8mm. The surface area of each sample
is 0.282 mm2, or in pathologists’ terms, about the size of
2-3 high power fields. The number of spots on a single slide
is variable depending on the array design, the current comfortable
maximum with the 0.6 mm needle is about 600 spots per standard
glass microscope slide. New technologies are under development
that may allow as many as 2000 or more sections per slide.
Using this method, an entire cohort of cases can be analyzed
by staining just one or two master array slides, instead
of staining hundreds of conventional slides, yet each spot
on the array is similar to a conventional slide in that complete
demographic and outcome information is maintained for each
case so that rigorous statistical analysis can be done as
rapidly as the arrays are analyzed.
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