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Head and Neck Pathology
Published in: Head and Neck Pathology 3/2019

01-09-2019 | Original Paper

Identifying Candidate Biomarkers for Pleomorphic Adenoma: A Case–Control Study

Authors: Matthew D. Morrison, Linda Jackson-Boeters, Zia A. Khan, Michael S. Shimizu, Jason H. Franklin, Kevin Fung, John H. J. Yoo, Mark R. Darling

Published in: Head and Neck Pathology | Issue 3/2019

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Abstract

Pleomorphic adenoma (PA) is the most common benign salivary gland tumor. Kallikrein-related peptidases have been identified as biomarkers in many human tumors and may influence tumor behavior. We investigated KLK1−15 messenger ribonucleic acid and proteins in PA specimens to determine a KLK expression profile for this tumor. Fresh frozen PA tissue specimens (n = 26) and matched controls were subjected to quantitative real-time reverse transcription polymerase chain reaction to detect KLK1−15 mRNA. Expression of KLK1, KLK12, KLK13, and KLK8 proteins were then evaluated via immunostaining techniques. Statistical analyses were performed with the level of significance set at P < .05. We observed downregulation of KLK1, KLK12, and KLK13 mRNA expression, and immunostaining studies revealed downregulation of the corresponding proteins. Histologic evidence of capsular perforation was associated with increased KLK1 protein expression. Tumor size was not associated with capsular invasion and/or perforation. This study is the first to detail a KLK expression profile for PA at both the transcriptional level and the protein level. Future work is required to develop clinical applications of these findings.
Literature
1.
Spiro RH. Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg. 1986;8:177–84.CrossRef
2.
Hellquist H, Skalova A. Histopathology of salivary glands. Berlin: Springer; 2014.CrossRef
3.
Neville BW, Damm DD, Allen CM, Bouquot JE, editors. Oral and maxillofacial pathology. 3rd ed. St. Louis: WB Saunders; 2009.
4.
Mito JK, Jo VY, Chiosea SI, et al. HMGA2 is a specific immunohistochemical marker for pleomorphic adenoma and carcinoma ex-pleomorphic adenoma. Histopathology 2017;71(4):511–21.CrossRef
5.
Yousef GM, Diamandis EP. The expanded human kallikrein gene family: locus characterization and molecular cloning of a new member, KLK-L3 (KLK9). Genomics 2000;65(2):184–94.CrossRef
6.
Clements J, et al. The expanded human kallikrein (KLK) gene family: genomic organisation, tissue-specific expression and potential functions. Biol Chem. 2001;382(1):5–14.CrossRef
7.
Harvey TJ, et al. Tissue specific expression patterns and fine mapping of the human kallikrein (KLK) locus on proximal 19q13.4. J Biol Chem. 2000;275(48):37397–406.CrossRef
8.
Clements JA, et al. The tissue kallikrein family of serine proteases: functional roles in human disease and potential as clinical biomarkers. Crit Rev Clin Lab Sci. 2004;41(3):265–312.CrossRef
9.
Prassas L, et al. Unleashing the therapeutic potential of human kallikrein-related serine proteases. Nat Rev Drug Discov. 2015;14(3):183–202.CrossRef
10.
Bartlett JD, Simmer JP. Kallikrein-related peptidase-4 (KLK4): role in enamel formation and revelations from ablated mice. Front Physiol. 2014;5:240.CrossRef
11.
Batra J, et al. Genetic polymorphisms in the human tissue kallikrein (KLK) locus and their implication in various malignant and non-malignant diseases. Biol Chem. 2012;393(12):1365–90.CrossRef
12.
Chao J, et al. Tissue kallikrein in cardiovascular, cerebrovascular and renal diseases and skin wound healing. Biol Chem. 2010;391(4):345–55.CrossRef
13.
Fischer J, Meyer-Hoffert U. Regulation of kallikrein-related peptidases in the skin from physiology to diseases to therapeutic options. Thromb Haemost. 2013;110(3):442–9.CrossRef
14.
Sotiropoulou G, Pampalakis G. Kallikrein-related peptidases: bridges between immune functions and extracellular matrix degradation. Biol Chem. 2010;391(4):321–31.CrossRef
15.
Yousef GM, Diamandis EP. Expanded human tissue kallikrein family novel panel of cancer biomarkers. Tumour Biol. 2002;23(3):185–92.CrossRef
16.
Diamandis EP, Yousef GM, Luo LY, Magklara A, Obiezu CV. The human kallikrein gene family—implications in carcinogenesis. Trends Endocrinol Metab. 2000;11:54–60.CrossRef
17.
Yousef GM, Diamandis EP. The new human tissue kallikrein gene family: Structure, function and association to disease. Endocr Rev. 2001;22:184–204.PubMed
18.
James GK, Pudek M, Berean KW, Diamandis EP, Archibald BL. Salivary duct carcinoma secreting prostate-specific antigen. Am J Clin Pathol. 1996;106:242–7.CrossRef
19.
Diamandis EP, Yousef GM. Human tissue kallikreins: a family of new cancer biomarkers. Clin Chem. 2002;48:1198–205.PubMed
20.
Diamandis EP, Yousef GM. Human tissue kallikrein gene family: a rich source of novel disease biomarkers. Expert Rev Mol Diagn. 2001;1:182–90.CrossRef
21.
Obiezu C, Diamandis E. Human tissue kallikrein family: applications in cancer. Cancer Lett. 2005;224:1–22.CrossRef
22.
Ellis GL, Auclair PL, Gnepp DR. Surgical pathology of the salivary glands. Philadelphia: W.B. Saunders Company; 1991.
23.
Davies L, Welch HG. Epidemiology of head and neck cancer in the United States. Otolaryngol Head Neck Surg. 2006;135:451–7.CrossRef
24.
Aro K, Leivo I, Makitie AA. Management and outcome of patients with mucoepidermoid carcinoma of major salivary gland origin: a single institution’s 30-year experience. Laryngoscope 2008;118:258–62.CrossRef
25.
Borgono CA, Diamandis EP. The emerging roles of human tissue kallikreins in cancer. Nat Rev Cancer. 2004;4:876–90.CrossRef
26.
Darling MR, et al. Human kallikrein 6 expression in salivary gland tumors. J Histochem Cytochem. 2006;54:337–42.CrossRef
27.
Hashem NN, et al. Kallikrein-related peptidase 7 in salivary gland tumours: immunohistochemical expression profile. Can J Pathol. 2011;3(3):12–9.
28.
Darling MR, et al. Human kallikrein 8 expression in salivary gland tumors. Head Neck Pathol. 2008;2:169–74.CrossRef
29.
Darling MR, et al. Kallikrein-related peptidase 10 expression in salivary gland tissues and tumours. Int J Biol Mark. 2012;27(4):e381–8.CrossRef
30.
Petraki CD, Karavana VN, Diamandis EP. Human tissues kallikrein 13 expression in normal tissues: an immunohistochemical study. J Histochem Cytochem. 2003;51:493–501.CrossRef
31.
Darling MR, Jackson-Boeters L, Daley TD, Diamandis EP. Human kallikrein 13 expression in salivary gland tumors. Int J Biol Mark. 2006;21(2):106–10.CrossRef
32.
Hashem NN, et al. Human kallikrein 14 (KLK14) expression in salivary gland tumors. Int J Biol Mark. 2010;25:32–7.CrossRef
33.
Darling MR, et al. Human kallikrein 3 (prostate-specific antigen) and human kallikrein 5 expression in salivary gland tumors. Int J Biol Mark. 2006;21(4):201–5.
34.
Barnes L, Eveson J, Reichart P, Sidransky D. World Health Organization classification of tumours. Pathology and genetics of head and neck tumours. Lyon: International Agency for Research on Cancer (IARC) Press; 2005.
35.
Culling CFA. Handbook of histopathological and histochemical techniques. 3rd ed. Oxford: Butterworth-Heinemann; 1974.
36.
Shaw JL, Diamandis EP. Distribution of 15 human kallikreins in tissues and biological fluids. Clin Chem. 2007;53(8):1423–32.CrossRef
37.
Eissa A, Diamandis EP. Human tissue kallikreins as promiscuous modulators of homeostatic skin barrier functions. Biol Chem. 2008;389:669–80.CrossRef
38.
Emami N, Diamandis EP. New insights into the functional mechanisms and clinical applications of the kallikrein-related peptidase family. Mol Oncol. 2007;1:269–87.CrossRef
39.
Borgono CA, Michael IP, Diamandis EP. Human tissue kallikreins: physiologic roles and applications in cancer. Mol Cancer Res. 2004;2:257–80.PubMed
40.
Sotiropoulou G, Pampalakis G, Diamandis EP. Functional roles of human kallikrein-related peptidases. J Biol Chem. 2009;284:32989–94.CrossRef
41.
Meyer-Hoffert U, Wu Z, Kantyka T, et al. Isolation of SPINK6 in human skin selective inhibitor of kallikrein-related peptidases. J Biol Chem. 2010;285(42):32174–81.CrossRef
42.
Bhoola KD, et al. Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol Rev. 1992;44:1–80.PubMed
43.
Madeddu P, Emanueli C, El-Dahr S. Mechanisms of disease: the tissue kallikrein-kinin system in hypertension and vascular remodeling. Nat Clin Pract Nephrol. 2007;3:208–21.CrossRef
44.
Yayama K, et al. Tissue kallikrein is synthesized and secreted by human vascular endothelial cells. Biochim Biophys Acta. 2003;1593:231–8.CrossRef
45.
Dedio J, et al. Tissue kallikrein KLK1 is expressed de novo in endothelial cells and mediates relaxation of human umbilical veins. Biol Chem. 2001;382:1483–90.CrossRef
46.
Li XS, He XL. Kallikrein 12 downregulation reduces AGS gastric cancer cell proliferation and migration. Genet Mol Res. 2016;15(3):gmr.15038452.
47.
Kapadia C, Yousef GM, Mellati AA, et al. Complex formation between human kallikrein 13 and serum protease inhibitors. Clin Chim Acta. 2004;339:157–67.CrossRef
48.
Kantyka T, Fischer J, Wu ZH, et al. Inhibition of kallikrein-related peptidases by the serine protease inhibitor of Kazal-type 6. Peptides 2011;32(6):1187–1192.CrossRef
49.
Ishige S, Kasamatsu A, Ogoshi K, et al. Decreased expression of kalllikrein-related peptidase 13: possible contribution to metastasis of human oral cancer. Mol Carcinogen. 2014;53(7):557–65.CrossRef
50.
Kapadia C, Ghosh MC, Grass L, Diamandis EP. Human kallikrein 13 involvement in extracellular matrix degradation. Biochem Biophys Res Commun. 2004;323:1084–90.CrossRef
51.
Rosai J, Ackerman LV. Rosai and Ackerman’s surgical pathology. 10th ed. Edinburgh: Mosby; 2011.
52.
Vercelli-Retta J, Almeida E, Ardao G, et al. Capsular pseudoinvasion after fine-needle aspiration of follicular adenomas of the thyroid. Diagn Cytopathol. 1997;17(4):295–7.CrossRef
53.
van Krieken JHJM. Prostate marker immunoreactivity in salivary gland neoplasms. Am J Surg Pathol. 1993;17(4):410–4.CrossRef
Metadata
Title
Identifying Candidate Biomarkers for Pleomorphic Adenoma: A Case–Control Study
Authors
Matthew D. Morrison
Linda Jackson-Boeters
Zia A. Khan
Michael S. Shimizu
Jason H. Franklin
Kevin Fung
John H. J. Yoo
Mark R. Darling
Publication date
01-09-2019
Publisher
Springer US
Published in
Head and Neck Pathology / Issue 3/2019
Electronic ISSN: 1936-0568
DOI
https://doi.org/10.1007/s12105-018-0959-6

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