
Tissue microarrays (also TMAs) consist of
paraffin blocks in which up to 1000 separate
tissue cores are assembled in array fashion to allow
multiplex histological analysis
Histology,
also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...
.
History
The major limitations in molecular
clinical analysis of tissues include the cumbersome nature of procedures, limited availability of
diagnostic
Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine " cause and effect". In systems engine ...
reagents
In chemistry, a reagent ( ) or analytical reagent is a substance or compound added to a system to cause a chemical reaction, or test if one occurs. The terms ''reactant'' and ''reagent'' are often used interchangeably, but reactant specifies a ...
and limited patient sample size. The technique of tissue microarray was developed to address these issues.
Multi-tissue blocks were first introduced by H. Battifora in 1986 with his so-called “multitumor (sausage) tissue block" and modified in 1990 with its improvement, "the checkerboard tissue block" . In 1998, J. Kononen and collaborators developed the current technique, which uses a novel sampling approach to produce tissues of regular size and shape that can be more densely and precisely arrayed.
Procedure
In the tissue microarray technique, a hollow needle is used to remove tissue cores as small as 0.6 mm in diameter from regions of interest in paraffin-embedded tissues such as clinical
biopsies
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a di ...
or
tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
samples. These tissue cores are then inserted in a recipient paraffin block in a precisely spaced, array pattern.
Sections
Section, Sectioning or Sectioned may refer to:
Arts, entertainment and media
* Section (music), a complete, but not independent, musical idea
* Section (typography), a subdivision, especially of a chapter, in books and documents
** Section sig ...
from this block are cut using a
microtome
A microtome (from the Greek ''mikros'', meaning "small", and ''temnein'', meaning "to cut") is a cutting tool used to produce extremely thin slices of material known as ''sections''. Important in science, microtomes are used in microscopy, allow ...
, mounted on a microscope slide and then analyzed by any method of standard histological analysis. Each microarray block can be cut into 100 – 500 sections, which can be subjected to independent tests. Tests commonly employed in tissue microarray include
immunohistochemistry
Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to a ...
, and
fluorescent in situ hybridization. Tissue microarrays are particularly useful in analysis of
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
samples.
One variation is a
Frozen tissue array.
Use in research
The use of tissue microarrays in combination with
immunohistochemistry
Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to a ...
has been a preferred method to study and validate cancer biomarkers in various defined cancer
patient cohorts. The possibility to assemble a large number of representative cancer samples from a defined patient cohort that also has a corresponding clinical database, provides a powerful resource to study how different protein expression patterns correlate with different clinical parameters. Since patient samples are assembled into the same block, sections can be stained with the same protocol to avoid experimental variability and technical artefacts. Clinical cancer patient cohorts and corresponding tissue microarray sets have been used to study diagnostic, prognostic and treatment predictive
cancer biomarkers in most forms of cancer, including lung, breast, colorectal and renal cell cancer.
Immunohistochemistry combined with tissue microarrays has also been used with success in large scale efforts to create a map of protein expression on a more global scale.
See also
*
Cytomics
Cytomics is the study of cell biology ( cytology) and biochemistry in cellular systems at the single cell level. It combines all the bioinformatic knowledge to attempt to understand the molecular architecture and functionality of the cell system ( ...
References
* Battifora H: The multitumor (sausage) tissue block: novel method for immunohistochemical antibody testing. Lab Invest 1986, 55:244-248.
* Battifora H, Mehta P: The checkerboard tissue block. An improved multitissue control block. Lab Invest 1990, 63:722-724.
* Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP: Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 1998, 4:844-847.
External links
*{{Commonscat-inline
National Cancer Institute Tissue Array Research Program
Tissues (biology)
Microarrays