Tissue microarray technology, TMA

Tissue microarray technology was introduced in 1998 by Kononen1, allowing hundreds of samples to be arrayed and studied in a single tissue block. The question arises as to whether the small cores present in the arrays are representative. The extent to which one, two, three or more cores will prove representative will vary with the heterogeneity of a particular tumour in its immunoreactivity for a particular antibody. The probability that any particular number of cores will be representative of the entire section has been studied:

Others have recommended the evaluation of 3 or 4 cores5,9.

Good correlation between TMAs and whole sections has been shown for a panel of lymphoid markers10 and for adipocytic tumours12.

The small size of bone marrow trephine cores and the presence of bone trabeculae does not preclude the construction of TMAs from cases of acute leukaemia: a concordance of 100% with full tissue sections has been demonstrated11.

The low rate of positivity of renal oncocytomas for kidney-specific cadherin in TMAs14 compared to conventional sections13 may be due to tumour heterogeneity.

Any limitation due to the sampling error in using cores to represent an entire section of a tumour is more than offset by the statistical advantage of being able to examine a very large number of cases of a particular tumour. For example, if 50% of 100 tumours are found to be immunoreactive, the 95% confidence interval for the true rate of reactivity for the population from which this sample is drawn is 40% to 60%. Most studies are of far smaller numbers of cases, and therefore the confidence intervals are correspondingly much wider.

References

1 Kononen, J., L. Bubendorf, et al. (1998). "Tissue microarrays for high-throughput molecular profiling of tumor specimens." Nat Med 4(7): 844-7.

2 Rosen, D. G., X. Huang, et al. (2004). "Validation of tissue microarray technology in ovarian carcinoma." Mod Pathol 17(7): 790-7.

3 Camp, R. L., L. A. Charette, et al. (2000). "Validation of tissue microarray technology in breast carcinoma." Lab Invest 80(12): 1943-9.

4 Gulmann, C., D. Butler, et al. (2003). "Biopsy of a biopsy: validation of immunoprofiling in gastric cancer biopsy tissue microarrays." Histopathology 42(1): 70-6.

5 Fernebro, E., M. Dictor, et al. (2002). "Evaluation of the tissue microarray technique for immunohistochemical analysis in rectal cancer." Arch Pathol Lab Med 126(6): 702-5.

6 Bubendorf, L., A. Nocito, et al. (2001). "Tissue microarray (TMA) technology: miniaturized pathology archives for high-throughput in situ studies." J Pathol 195(1): 72-9.

7 Hoos, A., M. J. Urist, et al. (2001). "Validation of tissue microarrays for immunohistochemical profiling of cancer specimens using the example of human fibroblastic tumors." Am J Pathol 158(4): 1245-51.

8 Gillett, C. E., R. J. Springall, et al. (2000). "Multiple tissue core arrays in histopathology research: a validation study." J Pathol 192(4): 549-53.

9 Rubin, M. A., R. Dunn, et al. (2002). "Tissue microarray sampling strategy for prostate cancer biomarker analysis." Am J Surg Pathol 26(3): 312-9.

10 Hedvat CV, Hegde A, Chaganti RS, et al. Application of tissue microarray technology to the study of non-Hodgkin's and Hodgkin's lymphoma. Hum Pathol 2002; 33:968-74

11 Zimpfer A, Schonberg S, Lugli A, et al. Construction and validation of a bone marrow tissue microarray. J Clin Pathol 2007; 60:57-61

12 Binh MB, Garau XS, Guillou L, et al. Reproducibility of MDM2 and CDK4 staining in soft tissue tumors. Am J Clin Pathol 2006; 125:693-7

13 Kuehn A, Paner GP, Skinnider BF, et al. Expression analysis of kidney-specific cadherin in a wide spectrum of traditional and newly recognized renal epithelial neoplasms: diagnostic and histogenetic implications. Am J Surg Pathol 2007; 31:1528-33

14 Mazal PR, Exner M, Haitel A, et al. Expression of kidney-specific cadherin distinguishes chromophobe renal cell carcinoma from renal oncocytoma. Hum Pathol 2005; 36:22-8

This page last revised 20.1.2007.

©SMUHT/PW Bishop