Tissue microarrays in clinical oncology

Abstract

Tissue microarray (TMA) is a recently implemented, high-throughput technology for the analysis of molecular markers in oncology. This research tool permits the rapid assessment of a biomarker in thousands of tumor samples, using commonly available laboratory assays such as immunohistochemistry and in situ hybridization. Although introduced less than a decade ago, TMA has proven to be invaluable in the study of tumor biology, the development of diagnostic tests, and the investigation of oncologic biomarkers. This review describes the impact of TMA-based research in clinical oncology and its potential future applications. Technical aspects of TMA construction and the advantages and disadvantages inherent to this technology are also discussed.

Figures

Figure 1

Tissue microarray planning. (A) Archival blocks are assembled and a surgical pathologist reviews the H&E slide for each case. The pathologist then circles the area of the block, localizing a representative tumor region from which a core will be extracted. (B) A sector map is designed; this is a grid that specifies a location within the TMA for each core sample. The sector map is then used to guide TMA construction and subsequent scoring, and it links biomarker scores to clinicopathological data on each case.

Figure 2

Tissue microarray construction and staining. (A) Beecher Instruments Microarrayer. The main components of the microarrayer are 2 hollow needles with stylets, a magnetic paraffin block holder, and positioning micrometers. (B) “Donor” block following extraction of triplicate 0.6 mm cores. The representative tumor region has been circled with a marker, and the cores were extracted from this area. (C) Completed TMA “recipient” block comprised of 300 cores.

Figure 3

Scoring the TMA. (A) Example of a TMA scoring workstation with multiple displays. The TMA is best displayed concurrently at low magnification for orientation and unambiguous core assignment, and high magnification for scoring. (B) Sample of a TMA core under high magnification. This is a core from a breast adenocarcinoma that has been stained for estrogen receptors. (C) The TMA under low magnification.

Figure 4

Immunohistochemistry can improve pathological diagnosis. Immunohistochemistry plays an important role in differentiating between gastrointestinal leiomyosarcoma (A) and gastrointestinal stromal tumor (GIST) (B). Desmin immunostaining is positive in leiomyosarcoma (C) but negative in GIST (D). Conversely C-Kit immunostaining is negative in leiomyosarcoma (E) and positive in GIST (F).

Figure 5

TMAs in laboratory medicine. Using a large tissue microarray, 2 estrogen receptor (ER) antibodies were assessed on more than 4000 invasive breast cancer tumors. It was found that the novel SP1 antibody was 8% more sensitive and equally specific as compared to the more commonly used 1D5 antibody. This breast cancer tumor would be classified ER negative with 1D5 (A) but is strongly positive with SP1 (B).