Skip to main content
Log in

Human Tissue Kallikreins in Polymorphous Adenocarcinoma: A Polymerase Chain Reaction and Immunohistochemical Study

  • Original Paper
  • Published:
Head and Neck Pathology Aims and scope Submit manuscript

Abstract

Polymorphous adenocarcinoma (PAC) is the second most common malignant salivary gland tumour of minor salivary glands. Human tissue kallikreins (KLKs) are a family of highly conserved serine proteases expressed by various tissues and organs. The literature demonstrates a link between KLKs and salivary gland neoplasms. The purpose of this study was to determine levels of KLK mRNA in tissue samples of PAC and to determine if KLK expression is limited to tumour cells. Nineteen cases of PAC were reviewed (1987–2013). The diagnosis was confirmed, demographic data was collected, and formalin fixed paraffin-embedded PAC and normal salivary gland tissue samples were obtained. RNA isolation was achieved, followed by conversion to complementary DNA via reverse transcription. Using PCR, the quantitative level of expression of KLKs1–15 was recorded. Samples exhibiting high and low KLK expression were selected for immunohistochemistry staining. Results revealed a statistically significant increase in mean KLK mRNA expression for KLK1, KLK4, KLK10, KLK12 and KLK15 in PAC tissue samples, compared with normal salivary gland tissue (Mann–Whitney U test, p < 0.05). Immunohistochemistry results demonstrated that KLKs were present in tumor cells. Notably, all samples demonstrating relatively higher KLK mRNA expression showed equivalent or increased staining scores relative to the low KLK mRNA expression samples. In conclusion, there appears to be aberrant kallikrein expression in polymorphous adenocarcinoma, suggesting the possibility of a kallikrein cascade influence on tumor development and progression.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Neville BW, Damm DD, Allen CM, Chi AC. Oral and maxillofacial pathology. 4th ed. St. Louis: Elsevier; 2016. p. 422–72.

    Google Scholar 

  2. Fonseca I, Assaad A, Katabi N, Seethala R, Weinreb I, Wenig BM. Polymorphous adenocarcinoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takashi T, Slootweg PJ, editors. WHO classification of head and neck tumours. 4th ed. Lyon: International Agency for Research on Cancer; 2017. p. 167–8.

    Google Scholar 

  3. Chi AC, Neville BW. Surface papillary epithelial hyperplasia (rough mucosa) is a helpful clue for identification of polymorphous low-grade adenocarcinoma. Head Neck Pathol. 2015;9:244–52.

    Article  Google Scholar 

  4. Rooper L, Sharma R, Bishop JA. Polymorphous low grade adenocarcinoma has a consistent p63+/p40− immunophenotype that helps distinguish it from adenoid cystic carcinoma and cellular pleomorphic adenoma. Head Neck Pathol. 2015;9:79–84.

    Article  Google Scholar 

  5. Persson F, Fehr A, Sundelin K, Schulte B, Lon̈ing T, Stenman G. Studies of genomic imbalances and the MYB-NFIB gene fusion in polymorphous low-grade adenocarcinoma of the head and neck. Int J Oncol. 2012;40:80–4.

    CAS  PubMed  Google Scholar 

  6. Weinreb I, Zhang L, Tirunagari LMS, Sung YS, Chen CL, Perez-Ordonez B, et al. Novel PRKD gene rearrangements and variant fusions in cribriform adenocarcinoma of salivary gland origin. Genes Chromosome Cancer. 2014;53:845–56.

    Article  CAS  Google Scholar 

  7. Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010;5(6):463–6.

    Article  Google Scholar 

  8. Kontos CK, Scorilas A. Kallikrein-related peptidases (KLKs): a gene family novel cancer biomarkers. Clin Chem Lab Med. 2012;50:1877–91.

    Article  CAS  Google Scholar 

  9. Obiezu CV, Diamandis EP. Human tissue kallikrein gene family: applications in cancer. Cancer Lett. 2005;224(1):1–22.

    Article  CAS  Google Scholar 

  10. Pavlopoulou A, Pampalakis G, Michalopoulos I, Sotiropoulou G. Evolutionary history of tissue kallikreins. PLoS ONE. 2010;5(11):e13781.

    Article  Google Scholar 

  11. Sotiropoulou G, Pampalakis G, Diamandis EP. Functional roles of human Kallikrein-related peptidases. J Biol Chem. 2009;284(48):32989–94.

    Article  CAS  Google Scholar 

  12. Yousef GM, Scorilas A, Katsaros D, Fracchioli S, Iskander L, Borgono C, et al. Prognostic value of the human kallikrein gene 15 expression in ovarian cancer. J Clin Oncol. 2003;21:3119–266.

    Article  CAS  Google Scholar 

  13. Borgoño CA, Grass L, Soosaipillai A, Yousef GM, Petraki CD, Howarth DHC, et al. Human kallikrein 14: a new potential biomarker for ovarian and breast cancer. Cancer Res. 2003;63:9032–41.

    PubMed  Google Scholar 

  14. Yousef GM, Polymeris M-E, Grass L, Soosaipillai A, Chan P-C, Scorilas A, et al. Human kallikrein 5: a potential novel serum biomarker for breast and ovarian cancer. Cancer Res. 2003;63:3958–65.

    CAS  PubMed  Google Scholar 

  15. Yousef GM, Diamandis EP. Kallikreins, steroid hormones and ovarian cancer: is there a link? Minerva Endocrinol. 2002;27:157–66.

    CAS  PubMed  Google Scholar 

  16. Emami N, Diamandis EP. Utility of kallikrein-related peptidases (KLKs) as cancer biomarkers. Clin Chem. 2008;54:1600–7.

    Article  CAS  Google Scholar 

  17. Yousef GM, Diamandis EP. Expanded human tissue kallikrein family—a novel panel of cancer biomarkers. Tumour Biol. 2002;23:185–92.

    Article  CAS  Google Scholar 

  18. Emami N, Diamandis EP. Potential role of multiple members of the kallikrein-related peptidase family of serine proteases in activating latent TGF beta 1 in semen. Biol Chem. 2010;391:85–95.

    Article  CAS  Google Scholar 

  19. Darling MR, Jackson-Boeters L, Daley TD, Diamandis EP. Human kallikrein 13 expression in salivary gland tumors. Int J Biol Markers. 2006;21:106–10.

    Article  CAS  Google Scholar 

  20. Darling MR, Tsai S, Jackson-Boeters L, Daley TD, Diamandis EP. Human kallikrein 8 expression in salivary gland tumors. Head Neck Pathol. 2008;2(3):169–74.

    Article  Google Scholar 

  21. Darling MR, Hashem NN, Zhang I, Mohamed ABD, Fung K, Kwan K, et al. Kallikrein-related peptidase 10 expression in salivary gland tissues and tumours. Int J Biol Markers. 2012;27:e381–e388388.

    Article  CAS  Google Scholar 

  22. Hashem NN, Mara TW, Mohamed M, Zhang I, Fung K, Kwan KF, et al. Human kallikrein 14 (KLK14) expression in salivary gland tumors. Int J Biol Markers. 2010;25:32–7.

    Article  CAS  Google Scholar 

  23. Kerr Z, Hayter A, Khan Z, Darling M. Kallikrein-related peptidase mRNA expression in adenoid cystic carcinoma of salivary glands: a polymerase chain reaction study. Head Neck Pathol. 2019. https://link.springer.com/10.1007/s12105-019-01076-4 (Epub ahead of print).

  24. Morrison MD, Jackson-Boeters L, Khan ZA, Shimizu MS, Franklin JH, Fung K, et al. Identifying candidate biomarkers for pleomorphic adenoma: a case–control study. Head Neck Pathol. 2019;13:286–97.

    Article  Google Scholar 

  25. Hashem N, Mohamed M, Zhang I, Fung K, Kwan K, Mara T, et al. Kallikrein-related peptidase 7 in salivary gland tumours: immunohistochemical profile. Can J Pathol. 2011;3:12–9.

    Google Scholar 

Download references

Funding

Dr. M. Darling was supported by Internal Research Grant, University of Western Ontario.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mark Darling.

Ethics declarations

Conflict of interest

The authors have no conflict of interest to declare.

Ethical Approval

Research involved formalin fixed paraffin embedded tissues only. This study was approved by the Western University Research and Ethics Board, Project ID 103783. The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cox, J., Khan, Z., Jackson-Boeters, L. et al. Human Tissue Kallikreins in Polymorphous Adenocarcinoma: A Polymerase Chain Reaction and Immunohistochemical Study. Head and Neck Pathol 15, 169–178 (2021). https://doi.org/10.1007/s12105-020-01196-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12105-020-01196-2

Keywords

Navigation