Skip to main content

Tissue Microarray for Biomarker Studies in Salivary Gland Tumors

Tissue Microarray and Salivary Gland Tumors

  • Living reference work entry
  • First Online:
Biomarkers in Cancer

Abstract

Tissue microarray (TMA) modern methodology was first described by Wan et al. in 1987, being further adapted by Kononen et al. in 1998 after which the technique became quickly and widely accepted and described in the scientific literature worldwide. Its development took place at a time which demanded maximum results in a minimum period of time that followed the onset of other important methodological approaches like cDNA microarray and proteomics. Hence, with this new technique intended to be used in association with paraffin-embedded neoplastic or nonneoplastic human tissues, the biomarkers recently described with the use of cDNA microarray and proteomics could be clinicopathologically validated on a large-scale basis. The main advantage of TMA methodology is related to its ability of aggregating hundreds of tumor samples from different cases in a single paraffin block. Despite its possible limitations with regard to tissue representation, numerous validation studies have demonstrated its statistical equivalence with conventional tissue sections, further supporting its use in the study of molecular biomarkers at a DNA, RNA, or protein level. Because of the scarce knowledge currently available regarding the molecular pathogenesis of salivary gland tumors, the use of a high-throughput technology like TMA in the investigation of such group of tumors becomes extremely interesting. As a consequence, we have witnessed an increase in the number of studies looking for new potentially useful biomarkers using TMA sections for better understanding of the etiopathogenesis of salivary gland tumors. In this chapter the authors aim to describe the laboratory and scientific advantages that TMA methodology has brought in recent decades, describing its most important characteristics and potential limitations, especially related to the study of biomarkers in the highly morphologically heterogeneous group of salivary gland tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

Similar content being viewed by others

Abbreviations

CD34:

Cluster of Differentiation 34

cDNA:

Complementary Deoxyribonucleic Acid

Mcm2:

Minichromosome Maintenance Complex Component 2

PCR:

Polymerase Chain Reaction

PLUNC:

Palate, Lung, and Nasal Epithelium Clone

RNA:

Ribonucleic Acid

TMA:

Tissue Microarray

References

  • Alkushi A. Validation of tissue microarray biomarker expression of breast carcinomas in Saudi women. Hematol Oncol Stem Cell Ther. 2009;2:394–8.

    Article  PubMed  Google Scholar 

  • Barnes L, Eveson JW, Reichart PA, et al. World health organization classification of tumours. Pathology and genetics of head and neck tumours. 1st ed. Lyon: IARC Press; 2005.

    Google Scholar 

  • Battifora H. The multitumor (sausage) tissue block: novel method for immunohistochemical antibody testing. Lab Invest. 1986;55:244–8.

    CAS  PubMed  Google Scholar 

  • Bhargava R, Lal P, Chen B. Feasibility of using tissue microarrays for the assessment of HER-2 gene amplification by fluorescence in situ hybridization in breast carcinoma. Diagn Mol Pathol. 2004;13:213–16.

    Article  CAS  PubMed  Google Scholar 

  • Boone J, van Hillegersberg R, van Diest PJ, et al. Validation of tissue microarray technology in squamous cell carcinoma of the esophagus. Virchows Arch. 2008;452:507–14.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Boos LA, Dettmer M, Schmitt A, et al. Diagnostic and prognostic implications of the PAX8–PPARγ translocation in thyroid carcinomas – a TMA-based study of 226 cases. Histopathology. 2013;63:234–41.

    Article  PubMed  Google Scholar 

  • Camp RL, Neumeister V, Rimm DL. A decade of tissue microarrays: progress in the discovery and validation of cancer biomarkers. J Clin Oncol. 2008;26:5630–7.

    Article  PubMed  Google Scholar 

  • Chen WC, Lin MS, Zhang BF, et al. Survey of molecular profiling during human colon cancer development and progression by immunohistochemical staining on tissue microarray. World J Gastroenterol. 2007;13:699–708.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Clauditz TS, Reiff M, Gravert L, et al. Human epidermal growth factor receptor 2 (HER2) in salivary gland carcinomas. Pathology. 2011;43:459–64.

    Article  CAS  PubMed  Google Scholar 

  • Datta MW, True LD, Nelson PS, et al. The role of tissue microarrays in prostate cancer biomarker discovery. Adv Anat Pathol. 2007;14:408–18.

    Article  CAS  PubMed  Google Scholar 

  • Eckel-Passow JE, Lohse CM, Sheinin Y, et al. Tissue microarrays: one size does not fit all. Diag Pathol. 2010;5:48.

    Article  Google Scholar 

  • El-Mansi MT, Williams ARW. Validation of tissue microarray technology using cervical adenocarcinoma and its precursors as a model system. Int J Gynecol Cancer. 2006;16:1225–33.

    Article  Google Scholar 

  • El-Mansi MT, Williams AR. Evaluation of PTEN expression in cervical adenocarcinoma by tissue microarray. Int J Gynecol Cancer. 2006;16(3):1254–60.

    Article  PubMed  Google Scholar 

  • Fons G, Hasibuan SM, van der Velden J, et al. Validation of tissue microarray technology in endometrioid cancer of the endometrium. J Clin Pathol. 2007;60:500–3.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fons G, van der Velden J, Burger M, et al. Validation of tissue microarray technology in vulvar cancer. Int J Gynecol Pathol. 2009;28:76–82.

    Article  PubMed  Google Scholar 

  • Fonseca FP, Carvalho MV, Almeida OP, et al. Clinicopathologic analysis of 493 cases of salivary gland tumors in a Southern Brazilian population. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;114:230–9.

    Article  PubMed  Google Scholar 

  • Fonseca FP, Rangel ALC, Almeida OP, et al. Tissue microarray construction for salivary gland tumors study. Med Oral Patol Oral Cir Bucal. 2013;18:e1–6.

    Article  Google Scholar 

  • Fonseca FP, Andrade BAB, Rangel ALCA, et al. Tissue microarray is a reliable method for immunohistochemical analysis of pleomorphic adenoma. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;117:81–8.

    Article  PubMed  Google Scholar 

  • Freier K, Flechtenmacher C, Walch A, et al. Differential KIT expression in histological subtypes of adenoid cystic carcinoma (ACC) of the salivary gland. Oral Oncol. 2005a;41:934–9.

    Article  CAS  PubMed  Google Scholar 

  • Freier K, Flechtenmacher C, Walchd A, et al. Copy number gains on 22q13 in adenoid cystic carcinoma of the salivary gland revealed by comparative genomic hybridization and tissue microarray analysis. Cancer Gen Cytogen. 2005b;159:89–95.

    Article  CAS  Google Scholar 

  • Gayed BA, Youssef RF, Bagrodia A, et al. Ki67 is an independent predictor of oncological outcomes in patients with localized clear-cell renal cell carcinoma. BJU Int. 2014;113(4):668–73.

    Google Scholar 

  • Glimelius I, Qvarnström F, Simonsson M, et al. Tissue microarray and digital image analysis: a methodological study with special reference to the microenvironment in Hodgkin lymphoma. Histopathology. 2012;61:26–32.

    Article  PubMed  Google Scholar 

  • Goldstine J, Seligson DB, Beizai P, et al. Tissue microarrays in the study of non-neoplastic disease of the nervous system. J Neuropathol Exp Neurol. 2002;61:653–62.

    PubMed  Google Scholar 

  • Ito FA, Ito K, Vargas PA, et al. Salivary gland tumors in a Brazilian population: a retrospective study of 496 cases. Int J Oral Maxillofac Surg. 2005;34:533–6.

    Article  CAS  PubMed  Google Scholar 

  • Iwafuchi H, Mori N, Takahashi T, et al. Phenotypic composition of salivary gland tumors: an application of principle component analysis to tissue microarray data. Mod Pathol. 2004;17:803–10.

    Article  CAS  PubMed  Google Scholar 

  • Kallioniemi O, Wagner U, Kononen J, et al. Tissue microarray technology for high-throughput molecular profiling of cancer. Human Mol Gen. 2001;10:657–62.

    Article  CAS  Google Scholar 

  • Karlsson C, Bodin L, Piehl-Aulin K, et al. Tissue microarray validation: a methodologic study with special reference to lung cancer. Cancer Epidemiol Biomarkers Prev. 2009;18:2014–21.

    Article  CAS  PubMed  Google Scholar 

  • Kononen J, Bubendorf L, Kallioniemi A, et al. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med. 1998;4:844–7.

    Article  CAS  PubMed  Google Scholar 

  • Ladstein RG, Bachmann IM, Straume O, et al. Ki67 expression is superior to mitotic count and novel proliferation markers PHH3, MCM4 and mitosin as a prognostic factor in thick cutaneous melanoma. BMC Cancer. 2010;10:140.

    Article  PubMed Central  PubMed  Google Scholar 

  • Lee HE, Han N, Kim MA, et al. DNA damage response-related proteins in gastric cancer: ATM, Chk2 and p53 expression and their prognostic value. Pathobiology. 2014;81:25–35.

    Article  CAS  PubMed  Google Scholar 

  • Madeira M, Mattar A, Logullo AF, et al. Estrogen receptor alpha/beta ratio and estrogen receptor beta as predictors of endocrine therapy responsiveness – a randomized neoadjuvant trial comparison between anastrozole and tamoxifen for the treatment of postmenopausal breast cancer. BMC Cancer. 2013;13:425.

    Article  PubMed Central  PubMed  Google Scholar 

  • Marques YMFS, Giudice FS, Freitas VM, et al. Oestrogen receptor b in adenoid cystic carcinoma of salivary glands. Histopathology. 2012;60:609–16.

    Article  PubMed  Google Scholar 

  • Nelhűbel GA, Károly B, Szabó B, et al. The prognostic role of claudins in head and neck squamous cell carcinomas. Pathol Oncol Res. 2014;20(1):99–106.

    Google Scholar 

  • Nocito A, Bubendorf L, Tinner EM, et al. Microarrays of bladder cancer tissue are highly representative of proliferation index and histological grade. J Pathol. 2001;194:349–57.

    Article  CAS  PubMed  Google Scholar 

  • Nowak M, Svensson MA, Carlsson J, et al. Prognostic significance of phospho-histone H3 in prostate carcinoma. World J Urol. 2014;32(3):703–7.

    Google Scholar 

  • Parsons M, Grabsch H. How to make tissue microarrays. Diagn Histopathol. 2009;15:142–50.

    Article  Google Scholar 

  • Radhakrishnan R, Solomon M, Satyamoorthy K, et al. Tissue microarray – a high-throughput molecular analysis in head and neck cancer. J Oral Pathol Med. 2008;37:166–76.

    Article  PubMed  Google Scholar 

  • Rosen DG, Huang X, Deavers MT, et al. Validation of tissue microarray technology in ovarian carcinoma. Modern Pathol. 2004;17:790–7.

    Article  CAS  Google Scholar 

  • Schneider S, Kloimstein P, Pammer J, et al. New diagnostic markers in salivary gland tumors. Eur Arch Otorhinolaryngol. 2014;271(7):1999–2007.

    Google Scholar 

  • Simon R, Sauter G. Tissue microarrays for miniaturized high-throughput molecular profiling of tumors. Exp Hematol. 2002;30:1365–72.

    Article  CAS  PubMed  Google Scholar 

  • Skirnisdottir I, Seidal T. Association of p21, p21 p27 and p21 p53 status to histological subtypes and prognosis in low-stage epithelial ovarian cancer. Cancer Genomics Proteomics. 2013;10:27–34.

    CAS  PubMed  Google Scholar 

  • Taylor CR. From microscopy to whole slide digital images: a century and a half of image analysis. Appl Immunohistochem Mol Morphol. 2011;19:491–3.

    Article  PubMed  Google Scholar 

  • Tennstedt P, Köster P, Brüchmann A, et al. The impact of the number of cores on tissue microarray studies investigating prostate cancer biomarkers. Int J Oncol. 2012;40:261–8.

    PubMed  Google Scholar 

  • Toberer F, Sykora J, Göttel D, et al. Apoptotic signal molecules in skin biopsies of cutaneous lupus erythematosus: analysis using tissue microarray. Exp Dermatol. 2013;22:656–9.

    Article  PubMed  Google Scholar 

  • Torhorst J, Bucher C, Kononen J, et al. Tissue microarray for rapid linking of molecular changes to clinical endpoints. Am J Pathol. 2001;159:2249–56.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • van de Rijn M, Gilks CB. Applications of microarrays to histopathology. Histopathology. 2004;44:97–108.

    Article  PubMed  Google Scholar 

  • van Zwieten A. Tissue microarray technology and findings for diagnostic immunohistochemistry. Pathology. 2013;45:71–9.

    Article  PubMed  Google Scholar 

  • Vargas PA, Gerhard R, Araújo Filho VJF, et al. Salivary gland tumors in a Brazilian population: a retrospective study of 124 cases. Rev Hosp Clín Fac Med S Paulo. 2002;57(6):271–6.

    PubMed  Google Scholar 

  • Vargas PA, Cheng Y, Barrett AW, et al. Expression of Mcm-2, Ki-67 and geminin in benign and malignant salivary gland tumours. J Oral Pathol Med. 2008a;37:309–18.

    Article  CAS  PubMed  Google Scholar 

  • Vargas PA, Speight PM, Bingle CD, et al. Expression of PLUNC family members in benign and malignant salivary gland tumours. Oral Dis. 2008b;14:613–19.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Voduc D, Kenney C, Nielsen TO. Tissue microarrays in clinical oncology. Semin Radiat Oncol. 2008;18:89–97.

    Article  PubMed Central  PubMed  Google Scholar 

  • Wan WH, Fortuna MB, Furmanski P. A rapid and efficient method for testing immunohistochemical reactivity of monoclonal antibodies against multiple tissue samples simultaneously. J Immunol Methods. 1987;103:121–9.

    Article  CAS  PubMed  Google Scholar 

  • Williams MD, Roberts DB, Kies MS, et al. Genetic and expression analysis of HER-2 and EGFR genes in salivary duct carcinoma: empirical and therapeutic significance. Clin Cancer Res. 2010;16:2266–74.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yamazaki M, Fujii S, Murata Y, et al. High expression level of geminin predicts a poor clinical outcome in salivary gland carcinomas. Histopathology. 2010;56:883–92.

    Article  PubMed  Google Scholar 

  • Zlobec I, Koelzer VH, Dawson H, et al. Next-generation tissue microarray (ngTMA) increases the quality of biomarker studies: an example using CD3, CD8, and CD45RO in the tumor microenvironment of six different solid tumor types. J Transl Med. 2013;11:104.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Pablo Agustin Vargas .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media Dordrecht

About this entry

Cite this entry

Vargas, P.A., Fonseca, F.P., de Almeida, O.P., Speight, P.M. (2014). Tissue Microarray for Biomarker Studies in Salivary Gland Tumors. In: Preedy, V., Patel, V. (eds) Biomarkers in Cancer. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7744-6_40-1

Download citation

  • DOI: https://doi.org/10.1007/978-94-007-7744-6_40-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Dordrecht

  • Online ISBN: 978-94-007-7744-6

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics