Tissue Microarrays

Tissue microarrays (TMAs) are collections of tumour samples, embedded in paraffin. They are used to find out whether proteins of interest are present in tumours, and to determine whether the presence of that protein can predict how the tumour will progress.

TMAs are analysed using a method called immunohistochemistry; this technique involves exposing the TMA to an antibody that recognises a specific protein. The antibody sticks to those cells within each sample that contain the protein of interest, and technicians can then use a label attached to the antibody to generate images of exactly where the protein is found within each tumour sample. Pathologists use these images to determine how much of each protein is present and in what percentage of the tumour cells, and even to see whether the protein is found on the outside surface of the tumour cells, or within the nucleus or other parts of the cell.

Assembling tumour samples into TMAs means that hundreds or even thousands of individual tumours can be rapidly assessed under identical experimental conditions. Researchers can then look for patterns in which tumours contain the protein, patterns that can help us predict how new patients with the same type of tumour will respond to treatment.

At the BC Cancer, part of the Provincial Health Services Authority (BC Cancer), every tumour sample within a TMA is linked to anonymised information about the patient who donated the sample: the type, stage and grade of the tumour; the treatment the patient received and how they responded to it; whether the cancer came back or moved to a new location after the original treatment ended; and other useful information. This is an incredibly valuable resource because it allows scientists to find correlations between the proteins found within tumours and how the tumour progresses in each patient.

For example, statistical analysis of the types of tumours that contain a given protein could tell us that:

  • patients whose tumours contain a certain protein respond better to a new drug than do patients whose tumours do not contain that protein. This information would help the BC Cancer’s oncologists decide which patients should be given which drugs.
  • tumours that contain a certain protein are more likely to come back after surgery. This information would help doctors decide which patients would benefit from follow-on treatments like radiation and/or chemotherapy, and which patients can be spared these treatments and the resulting side effects.

Researchers from the Department of Molecular Oncology use several different TMAs. For example, some TMAs contain breast tumours of all possible subtypes; other TMAs contain ovarian cancers of one specific type, or the cancers that are the most likely to come back after treatment. This allows us to answer different research questions. Some examples of the kind of work we’re doing with TMAs are given below.

Recent related papers from the Department of Molecular Oncology

  • Köbel M, Turbin D, Kalloger SE, Gao D, Huntsman DG, Gilks CB. Biomarker Expression in Pelvic High-grade Serous Carcinoma: Comparison of Ovarian and Omental Sites. Int J Gynecol Pathol. 2011: Epub ahead of print
  • Wiegand KC, Lee AF, Al-Agha OM, Chow C, Kalloger SE, Scott DW, Steidl C, Wiseman SM, Gascoyne RD, Gilks B, Huntsman DG. Loss of BAF250a (ARID1A) is frequent in high-grade endometrial carcinomas. J Pathol. 2011: doi: 10.1002/path.2911.
  • Kalloger SE, Köbel M, Leung S, Mehl E, Gao D, Marcon KM, Chow C, Clarke BA, Huntsman DG, Gilks CB. Calculator for ovarian carcinoma subtype prediction. Mod Pathol 2010 Dec 3. [Epub ahead of print]
  • Turashvili G, McKinney S, Goktepe O, Leung S, Huntsman D, Gelmon K, Los G, Rejto P, Aparicio S. P-cadherin expression as a prognostic biomarker in a 3 992 case tissue microarray series of breast cancer. Modern Pathology 2010 doi: 10.1038/modpathol.2010.189
  • Turashvili G, Leung S, Turbin D, Montgomery K, Gilks B, West R, Carrier M, Huntsman D, Aparicio S. Inter-observer reproducibility of HER2 immunohistochemical assessment and concordance with fluorescent in situ hybridization (FISH): pathologist assessment compared to quantitative image analysis. BMC Cancer 2009: 9:165
  • Prentice LM, Klausen C, Kalloger S, Koebel M, McKinney S, Santos JL, Kenney C, Mehl E, Gilks CB, Leung P, Swenerton K, Huntsman DG, Aparicio SA. Kisspeptin and GPR54 immunoreactivity in a cohort of 518 patients defines favourable prognosis and clear cell subtype in ovarian carcinoma BMC Medicine, 2007: 5(1):33
  • Dawson SJ, Makretsov N, Blows FM, Driver KE, Provenzano E, Le Quesne J, Baglietto L, Severi G, Giles GG, McLean CA, Callagy G, Green AR, Ellis I, Gelmon K, Turashvili G, Leung S, Aparicio S, Huntsman D, Caldas C, Pharoah P. BCL2 in breast cancer: a favourable prognostic marker across molecular subtypes and independent of adjuvant therapy received. Br J Cancer. 2010 doi: 10.1038/sj.bjc.6605736
  • Chiu CG, Masoudi H, Leung S, Voduc DK, Gilks B, Huntsman DG, Wiseman SM. HER-3 overexpression is prognostic of reduced breast cancer survival: a study of 4046 patients. Ann Surg 2010 251(6):1107-16.